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1
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Murao K, Kubo Y. Multiple Bowen Disease Lesions With the "Eyeliner Sign" in a Psoriasis Patient After Long-Term Narrow-Band Ultraviolet B Light Therapy. Am J Dermatopathol 2024; 46:193-194. [PMID: 38275222 DOI: 10.1097/dad.0000000000002634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Affiliation(s)
- Kazutoshi Murao
- Department of Dermatology, Tokushima University Graduate School of Biomedical Sciences, Japan
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2
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Sayuddin ENEN, Taher M, Arzmi MH, Burhanudin NA, Rostam MA. The role of podoplanin inhibitors in controlling oral cancer progression. Arch Oral Biol 2024; 157:105841. [PMID: 37952507 DOI: 10.1016/j.archoralbio.2023.105841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 10/17/2023] [Accepted: 10/29/2023] [Indexed: 11/14/2023]
Abstract
OBJECTIVE In this article, we review the current studies on the role of podoplanin in oral cancer and the potential application of podoplanin inhibitors as a therapeutic agent for oral cancer. DESIGN The narrative review approach was conducted, providing a comprehensive perspective of related literature. Publications addressing podoplanin and its inhibitors in the context of oral cancer were retrieved from PubMed and Scopus databases. RESULTS Podoplanin has emerged as a biomarker and therapeutic agent for oral cancer. Numerous studies have reported high podoplanin expression in oral cancer and pre-cancerous lesions compared to normal cells. A specific inhibitor targeting podoplanin may have the potential to prevent oral carcinogenesis via interfering with the pathway of cancerous cells involved in cell proliferation and metastasis. Antibodies, chimeric antigen receptor (CAR)-T cells, cancer-specific mAb (CasMab), synthetic molecules, and lectins are among the materials used as anticancer agents targeting podoplanin. Plant-derived lectins appear to demonstrate a unique advantage against alternative candidates. CONCLUSIONS The use of podoplanin inhibitors in place of existing therapeutic approaches could be a promising and novel approach to the prevention and treatment of oral cancer. Nevertheless, further research is required to investigate the practical application of such inhibitors.
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Affiliation(s)
- Engku Nasiha Engku Ngah Sayuddin
- Department of Nutrition Sciences, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Kuantan, Pahang, Malaysia
| | - Muhammad Taher
- Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang, Malaysia; Pharmaceutics and Translational Research Group, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang, Malaysia
| | - Mohd Hafiz Arzmi
- Department of Fundamental Dental and Medical Sciences, Kulliyyah of Dentistry, International Islamic University Malaysia, Kuantan, Pahang, Malaysia; Cluster of Cancer Research Initiative IIUM (COCRII), International Islamic University Malaysia, Kuantan, Pahang, Malaysia; Melbourne Dental School, The University of Melbourne, Victoria, Australia
| | - Nor Aszlitah Burhanudin
- Department of Oral Maxillofacial Surgery and Oral Diagnosis, Kulliyyah of Dentistry, International Islamic University Malaysia, Kuantan, Pahang, Malaysia
| | - Muhamad Ashraf Rostam
- Department of Nutrition Sciences, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Kuantan, Pahang, Malaysia; Cluster of Cancer Research Initiative IIUM (COCRII), International Islamic University Malaysia, Kuantan, Pahang, Malaysia.
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Sharma A, Natarajan S, Manaktala N, Boaz K, KP N, Lewis A, Yellapurkar S. Prognostic Nomogram for Lymph-Node Metastasis in Oral Squamous Cell Carcinoma (OSCC) Using Immunohistochemical Marker D2-40. Cancer Manag Res 2023; 15:929-936. [PMID: 37674659 PMCID: PMC10478775 DOI: 10.2147/cmar.s408772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Accepted: 07/24/2023] [Indexed: 09/08/2023] Open
Abstract
Introduction Nomograms are proven in "individualized risk prediction" in sarcomas and breast and prostate cancers. Incorporating immunohistochemical markers and histopathological parameters can enhance accuracy of these graphical representations of statistical predictive models concerning metastasis. D2-40, a monoclonal antibody to podoplanin (regulator of motility expressed in malignant epithelial cells), dually predicts metastatic potential of tumour by estimating the motile tumour phenotype and by detecting lymphatic vessels/density, both essential to metastasis in OSCC. Thus, we propose a model that incorporates D2-40 immunostaining of individual tumour cells (ITC) too with other variables (seen in H+E staining) as a predictive nomogram. Methods Sixty cases of OSCC were selected with equal number of cases (n=30) of pN0 and pN+ status. Bryne's grading of invasive front of tumour (ITF) was done on H+E-stained slides followed by D2-40 immunostaining for ITCs at ITF and lymphatic vessels. Multivariate regression analysis was used to generate the nomogram of LNM where the predictive contribution of each covariate, namely depth of invasion, D2-40-stained ITCs, gender, histological grade, and worst pattern of invasion (WPOI), was plotted on a scale of 1-100 points. Results The nomogram showed that the strongest variable in OSCC was the WPOI in H+E-stained section followed by D2-40-positive ITCs and gender. Discussion Our predictive nomogram for LNM in OSCC surprisingly showed that a tumour with lower score of WPOI (islands vs ITC) showed numerous D2-40-positive ITCs, drastically increasing the probability of metastasis. The concept of "individualized risk prediction" can be used to predict lymph node metastasis using a variety of histopathological criteria that can be visualized in routine and immunohistochemical staining in OSCC with the aid of a nomogram.
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Affiliation(s)
- Ankita Sharma
- Department of Oral Pathology, Manipal College of Dental Sciences Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Srikant Natarajan
- Department of Oral Pathology, Manipal College of Dental Sciences Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Nidhi Manaktala
- Department of Oral Pathology, Manipal College of Dental Sciences Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Karen Boaz
- Department of Oral Pathology, Manipal College of Dental Sciences Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Nandita KP
- Department of Oral Pathology, Manipal College of Dental Sciences Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Amitha Lewis
- Department of Oral Pathology, Manipal College of Dental Sciences Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Shweta Yellapurkar
- Department of Oral Pathology, Manipal College of Dental Sciences Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
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miR-532-3p inhibits the progression of tongue squamous cell carcinoma by targeting podoplanin. Chin Med J (Engl) 2021; 134:2999-3008. [PMID: 34939978 PMCID: PMC8710329 DOI: 10.1097/cm9.0000000000001563] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The association between miR-532-3p and tongue squamous cell carcinoma (TSCC) has been examined in the literature to improve the survival rate of patients with this tumor. However, further studies are needed to confirm the regulatory roles of this microRNA (miRNA) in TSCC. The objective of this study was to investigate the roles played by and the underlying mechanism used by the miR-532-3p/podoplanin (PDPN) axis in TSCC development. METHODS Western blotting and quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) were performed to evaluate the PDPN expression level in TSCC tissues and cells. The proliferative, adhesive, and migratory capabilities of TSCC cells (CAL-27 and CTSC-3) were examined using cell counting kit-8 (CCK-8), cell adhesion, and wound-healing assays, respectively. The dual-luciferase reporter (DLR) assay was later conducted to confirm the relationship between miR-532-3p and PDPN. RESULTS The results indicated that PDPN expression was enriched in TSCC tissues and cells, and that the expression of PDPN was associated with some clinicopathological parameters of TSCC, including lymph node metastasis (P = 0.001), tumor-node-metastasis (TNM) staging (P = 0.010), and grading (P = 0.010). Further analysis also showed that PDPN knockdown inhibited the viability, adhesive ability, and migratory capacity of CAL-27 and CTSC-3 cells, effects that could be reversed by the application of a miR-532-3p inhibitor. Additionally, PDPN was found to be a direct target of miR-532-3p. CONCLUSIONS This research suggested that by targeting PDPN, miR-532-3p could inhibit cell proliferation viability, adhesion, and migration in TSCC. Findings also revealed that the miR-532-3p/PDPN axis might provide more insights into the prognosis and treatment of TSCC.
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Warnecke-Eberz U, Plum P, Schweinsberg V, Drebber U, Bruns CJ, Müller DT, Hölscher AH, Bollschweiler E. Neoadjuvant chemoradiation changes podoplanin expression in esophageal cancer patients. World J Gastroenterol 2020; 26:3236-3248. [PMID: 32684738 PMCID: PMC7336324 DOI: 10.3748/wjg.v26.i23.3236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 04/20/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Locally advanced adenocarcinoma of the esophagus (EAC) and squamous cell carcinoma (ESCC) result in a worse prognosis. Neoadjuvant treatment improves survival, however, only for responders. The transmembrane glycoprotein podoplanin is overexpressed in squamous cell carcinomas, miRNA-363 is associated to its regulation in head and neck cancer.
AIM To predict therapy response and prognosis markers, and targets for novel therapies would individualize treatments leading to more favourable outcomes.
METHODS Expression of podoplanin protein has been visualized by immunohistochemistry in surgical specimens of 195 esophageal cancer patients who underwent transthoracic esophagectomy: 90 ESCC and 105 EAC with clinical T2-3, Nx, M0. One hundred and six patients received neoadjuvant chemoradiation. RNA was extracted from paraffin-embedded tissue, and miRNA-363 quantified by real-time TaqMan-real-time-PCR. D2-40 mab staining of > 5% was scored as high podoplanin expression (HPE). We related podoplanin and miRNA-363 expression to histopathologic response after neoadjuvant treatment and clinicopathological characteristics, such as histological tumor type, survival rate or clinical tumor category.
RESULTS We confirmed expression of membrane-bound podoplanin in 90 ESCC patients. 26% showed HPE of > 5%. In addition, absence in EAC patients (only 2% with HPE) was shown. Lower podoplanin expression has been detected in resection-specimen of 58 ESCC patients after neoadjuvant (RTx/CTx) treatment, only 11% with HPE, compared to 50% HPE of 32 non-pretreated primary surgery patients, P = 0.0001. This difference of podoplanin expression was confirmed comparing pre-treatment biopsies with matching post-treatment surgical specimens, P < 0.001. Podoplanin has been identified as a prognostic marker in 32 patients that underwent primary surgery without neoadjuvant treatment. Low (0-5%) podoplanin expression was associated with better prognosis compared to patients with HPE, P = 0.013. Podoplanin expression has been associated with post-transcriptional regulation by miRNA-363. At a cut-off value of miR-363 < 7, lower miR-363 expression correlated with HPE in surgical tissue specimens of primary surgery patients, P = 0.013. Therefore, ESCC patients with miRNA-363 expression < 7 had a worse prognosis than patients expressing miRNA-363 ≥ 7, P = 0.049.
CONCLUSION Analysis of the molecular process that leads to decrease in podoplanin expression during neoadjuvant treatment and its regulation may provide novel markers and targets to improve targeted therapy of ESCC.
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Affiliation(s)
- Ute Warnecke-Eberz
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne 50937, Germany
| | - Patrick Plum
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne 50937, Germany
| | - Viola Schweinsberg
- Department of Dermatology, University Hospital of Cologne, Cologne 50937, Germany
| | - Uta Drebber
- Institute of Pathology, University Hospital of Cologne, Cologne 50937, Germany
| | - Christiane J Bruns
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne 50937, Germany
| | - Dolores T Müller
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne 50937, Germany
| | | | - Elfriede Bollschweiler
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne 50937, Germany
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Voelker HU, Hintermeier I, Strehl A, Scheich M. Prognostic Potential of the Expression of Podoplanin (D2-40) Within Cells of Squamous Cell Carcinoma of the Larynx and Hypopharynx. World J Oncol 2020; 11:65-71. [PMID: 32284774 PMCID: PMC7141162 DOI: 10.14740/wjon1259] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 02/18/2020] [Indexed: 11/11/2022] Open
Abstract
Background Podoplanin (D2-20) stains immunohistochemically lymphatic vessels, regular mesothelium and tumor cells of different tumors, e.g. malignant mesothelioma or seminoma. In squamous cell carcinoma (SCC), the marker has been described as variously expressed. Methods This study has investigated the value of the immunohistochemical analysis for the prognostic relevance of the expression in 119 SCCs of the larynx and hypopharynx. The clinical data and documentation of follow-up for at least 5 years were available. Results The collective showed the expected distribution of patient age with accentuation of the male sex and a balanced spread of tumor stages including nodal status. The immunohistochemical stain intensity (negative, weak or strong) and the distribution (equal versus focal) were evaluated. In addition, the accentuation of the staining reaction was separately examined at the border of invasion. SCCs with a strong expression of podoplanin were associated with an unfavorable prognosis. A comparison of grouped cases showed a trend emerging with borderline results (negative to weakly positive, P = 0.51; negative to strongly positive, P = 0.054; weakly positive to strongly positive, P = 0.17). The staining at the border of invasion had no statistical effect on overall survival. Multivariate survival statistics however showed that lymphonodal metastasis and a reaction with podoplanin in tumor cells are associated with significant worse prognosis. Conclusion In summary, regardless of the exact function of podoplanin in the process of cell migration and tumor progression, an immunohistochemical identification of expression in tumor cells of SCC of the larynx and hypopharynx can give additional information about the expectable prognosis.
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Affiliation(s)
- Hans-Ullrich Voelker
- Department of Pathology, Leopoldina Krankenhaus GmbH, Gustav-Adolf-Str. 8, D-97422 Schweinfurt, Germany
| | - Isabelle Hintermeier
- Department of Pathology, Leopoldina Krankenhaus GmbH, Gustav-Adolf-Str. 8, D-97422 Schweinfurt, Germany
| | - Annette Strehl
- Department of Pathology, Leopoldina Krankenhaus GmbH, Gustav-Adolf-Str. 8, D-97422 Schweinfurt, Germany
| | - Matthias Scheich
- Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital of Wuerzburg, Josef-Schneider-Str. 2, D-97080 Wuerzburg, Germany
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Almahmoudi R, Kasanen M, Sieviläinen M, Salem A, Pirinen M, Salo T, Al-Samadi A. Prognostic value of blood and lymphatic vessel markers in tongue cancer: A systematic review. Cancer Sci 2019; 110:3424-3433. [PMID: 31495050 PMCID: PMC6824997 DOI: 10.1111/cas.14189] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 08/17/2019] [Accepted: 08/27/2019] [Indexed: 01/30/2023] Open
Abstract
Tongue squamous cell carcinoma (TSCC) has a poor prognosis due to its early metastasis through blood and lymphatic vessels. We undertook a systematic review to investigate the prognostic significance of blood microvessel density (MVD) and lymphatic vessel density (LVD) in TSCC patients. We carried out a systematic search in Ovid Medline, Scopus, and Cochrane libraries. All studies that evaluated the prognostic significance of MVD/LVD markers in TSCC were systematically retrieved. Our results showed that MVD/LVD markers, CD31, CD34, CD105, factor VIII, lymphatic vessel endothelial hyaluronan receptor‐1, and D2‐40 were evaluated in TSCC patients until 28 June 2018. Six out of 13 studies reported markers that were associated with poor prognosis in TSCC. Two out of three studies suggested that a high number of D2‐40+ vessels predicated low overall survival (OS); the third study reported that the ratio of D2‐40+ over factor VIII+ vessels is associated with low OS. Most of the other markers had controversial results for prognostication. We found higher expression of MVD/LVD markers were commonly, but not always, associated with shorter survival in TSCC patients. It is therefore not currently possible to recommend implementation of these markers as reliable prognosticators in clinical practice. More studies (especially for D2‐40) with larger patient cohorts are needed.
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Affiliation(s)
- Rabeia Almahmoudi
- Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.,Translational Immunology Research Program (TRIMM), University of Helsinki, Helsinki, Finland
| | - Merimaija Kasanen
- Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland
| | - Meri Sieviläinen
- Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland
| | - Abdelhakim Salem
- Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.,Translational Immunology Research Program (TRIMM), University of Helsinki, Helsinki, Finland
| | - Matti Pirinen
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.,Department of Public Health, University of Helsinki, Helsinki, Finland.,Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland
| | - Tuula Salo
- Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.,Translational Immunology Research Program (TRIMM), University of Helsinki, Helsinki, Finland.,Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.,Medical Research Centre, Oulu University Hospital, Oulu, Finland.,HUS, Helsinki University Hospital, Helsinki, Finland
| | - Ahmed Al-Samadi
- Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.,Translational Immunology Research Program (TRIMM), University of Helsinki, Helsinki, Finland
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Verma V, Chandrashekar C. Evaluation of SOX2 and podoplanin expression in oral epithelial dysplasia and its correlation with malignant transformation. ACTA ACUST UNITED AC 2019; 10:e12450. [PMID: 31464104 DOI: 10.1111/jicd.12450] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 07/18/2019] [Accepted: 07/29/2019] [Indexed: 12/14/2022]
Abstract
AIM Oral carcinogenesis cascade is a complex process, characterized by variable numbers of genetic and epigenetic alterations of various genes with manifold roles that could serve as biological hallmarks. This study was undertaken to assess the protein expression of SOX2 and podoplanin in oral epithelial dysplasia and correlate the expression with clinicopathological parameters and risk of malignant transformation. METHODS SOX2 and podoplanin expression were analyzed in 60 cases of oral epithelial dysplasia. The association between SOX2 and podoplanin expression with various clinicopathological parameters and transformation to oral cancer was analyzed. RESULTS A higher Histoscore was seen in 55% of moderate and 30% of severe dysplasia. 25% of the cases showed a negative podoplanin expression and 30% of patients had higher podoplanin expression (score 2 and 3). Though there was significant association of both SOX2 and podoplanin expression with the degree of dysplasia, the association of their expression with transformation to oral squamous cell carcinoma did not reach statistical significance. CONCLUSION Alteration in SOX2 and podoplanin is likely an important event in head and neck carcinogenesis; however, their expression may be valuable only in a few cases of oral epithelial dysplasia to assess the risk of malignant transformation.
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Affiliation(s)
- Vani Verma
- Department of Oral Pathology and Microbiology, Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Chetana Chandrashekar
- Department of Oral Pathology and Microbiology, Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal, India
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Karunagaran M, Murali P, Palaniappan V, Sivapathasundharam B. Expression and distribution pattern of podoplanin in oral submucous fibrosis with varying degrees of dysplasia – an immunohistochemical study. J Histotechnol 2019. [DOI: 10.1080/01478885.2019.1594543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- Monika Karunagaran
- Department of Oral Pathology & Microbiology, Saveetha Dental College & Hospital, SIMATS University, Chennai, India
| | - Preethi Murali
- Department of Oral Pathology & Microbiology, Meenakshi Ammal Dental College & Hospital, MAHER University, Chennai, India
| | - V. Palaniappan
- Department of Pathology, Chengalpattu Medical College, Chennai, India
| | - B. Sivapathasundharam
- Professor & Head, Department of Oral Pathology & Microbiology, Meenakshi Ammal Dental College & Hospital, MAHER University, Chennai, India
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10
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Grochau KJ, Safi AF, Drebber U, Grandoch A, Zöller JE, Kreppel M. Podoplanin expression in oral leukoplakia─a prospective study. J Craniomaxillofac Surg 2019; 47:505-509. [PMID: 30638740 DOI: 10.1016/j.jcms.2018.12.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 10/18/2018] [Accepted: 12/06/2018] [Indexed: 12/26/2022] Open
Abstract
PURPOSE The aim of this prospective work was to examine oral leukoplakia for their podoplanin expression to determine whether podoplanin expression is associated with the degree of dysplasia. MATERIALS AND METHODS We took biopsy samples from 50 patients with oral leukoplakia in 2013. The preparations studied by immunohistochemistry were analyzed in correlation with the degree of dysplasia and other clinicopathological variables. RESULTS The Chi-square test showed a significant correlation between podoplanin expression and the degree of dysplasia according to the squamous intraepithelial neoplasia (SIN) classification (p = 0.033). Also, a significant association between age grouping and podoplanin expression was found. We were able to show that the distribution is the same for both age groups in relation to the score of podoplanin expression (p = 0.003). CONCLUSION In a comparable retrospective work of our working group, it could be shown that podoplanin is a reliable predictive marker for the assessment of the risk of malignant transformation. The present work was able to substantiate the assumption that podoplanin not only plays an important role in the context of malignant degeneration but also exerts a major influence in advance.
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Affiliation(s)
- Kathrin J Grochau
- Department for Oral and Craniomaxillofacial Plastic Surgery, University of Cologne, Cologne, Germany.
| | - Ali-Farid Safi
- Department for Oral and Craniomaxillofacial Plastic Surgery, University of Cologne, Cologne, Germany
| | - Uta Drebber
- Department of Pathology, University of Cologne, Cologne, Germany
| | - Andrea Grandoch
- Department for Oral and Craniomaxillofacial Plastic Surgery, University of Cologne, Cologne, Germany
| | - Joachim E Zöller
- Department for Oral and Craniomaxillofacial Plastic Surgery, University of Cologne, Cologne, Germany
| | - Matthias Kreppel
- Department for Oral and Craniomaxillofacial Plastic Surgery, University of Cologne, Cologne, Germany
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11
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Retzbach EP, Sheehan SA, Nevel EM, Batra A, Phi T, Nguyen ATP, Kato Y, Baredes S, Fatahzadeh M, Shienbaum AJ, Goldberg GS. Podoplanin emerges as a functionally relevant oral cancer biomarker and therapeutic target. Oral Oncol 2018; 78:126-136. [PMID: 29496040 DOI: 10.1016/j.oraloncology.2018.01.011] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 12/14/2017] [Accepted: 01/18/2018] [Indexed: 12/22/2022]
Abstract
Oral cancer has become one of the most aggressive types of cancer, killing 140,000 people worldwide every year. Current treatments for oral cancer include surgery and radiation therapies. These procedures can be very effective; however, they can also drastically decrease the quality of life for survivors. New chemotherapeutic treatments are needed to more effectively combat oral cancer. The transmembrane receptor podoplanin (PDPN) has emerged as a functionally relevant oral cancer biomarker and chemotherapeutic target. PDPN expression promotes tumor cell migration leading to oral cancer invasion and metastasis. Here, we describe the role of PDPN in oral squamous cell carcinoma progression, and how it may be exploited to prevent and treat oral cancer.
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Affiliation(s)
- Edward P Retzbach
- Department of Molecular Biology and Graduate School of Biomedical Sciences, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA
| | - Stephanie A Sheehan
- Department of Molecular Biology and Graduate School of Biomedical Sciences, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA
| | - Evan M Nevel
- Department of Molecular Biology and Graduate School of Biomedical Sciences, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA
| | - Amber Batra
- Department of Molecular Biology and Graduate School of Biomedical Sciences, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA
| | - Tran Phi
- Department of Molecular Biology and Graduate School of Biomedical Sciences, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA
| | - Angels T P Nguyen
- Department of Molecular Biology and Graduate School of Biomedical Sciences, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA
| | - Yukinari Kato
- New Industry Creation Hatchery Center, Tohoku University; Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
| | - Soly Baredes
- Department of Otolaryngology-Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
| | - Mahnaz Fatahzadeh
- Department of Diagnostic Sciences, New Jersey School of Dental Medicine, Rutgers University, Newark, NJ 07103 USA
| | - Alan J Shienbaum
- Department of Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA
| | - Gary S Goldberg
- Department of Molecular Biology and Graduate School of Biomedical Sciences, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA.
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12
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Immunohistochemical Expression of Podoplanin in Clinical Variants of Oral Leukoplakia and Its Correlation With Epithelial Dysplasia. Appl Immunohistochem Mol Morphol 2018; 26:132-139. [DOI: 10.1097/pai.0000000000000383] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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13
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Barros FBA, Assao A, Garcia NG, Nonogaki S, Carvalho AL, Soares FA, Kowalski LP, Oliveira DT. Moesin expression by tumor cells is an unfavorable prognostic biomarker for oral cancer. BMC Cancer 2018; 18:53. [PMID: 29310601 PMCID: PMC5759236 DOI: 10.1186/s12885-017-3914-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 12/14/2017] [Indexed: 12/30/2022] Open
Abstract
Background Moesin is a member of the ERM (ezrin, radixin and moesin) proteins that participate in cell migration and tumor invasion through transductional signals sent to actin filaments by glycoproteins, such as podoplanin. Methods This study aimed to evaluate the participation of moesin and podoplanin in the invasive tumor front of oral squamous cell carcinomas, and their influence on patients’ prognosis. Podoplanin and moesin immunoexpressions were evaluated by a semi-quantitative score method, based on the capture of 10 microscopic fields, at 400X magnification, in the invasive tumor front of oral squamous cell carcinomas. The association of moesin and podoplanin expression with clinicopathological variables was analyzed by the chi-square, or Fisher’s exact test. The 5 and 10 years survival rates were calculated by the Kaplan-Meier method and the survival curves were compared by using the log-rank test. Results The immunohistochemical expression of moesin in the invasive front of oral squamous cell carcinomas was predominantly strong, homogenously distributed on the membrane and in the cytoplasm of tumor cells. The expression of moesin was not associated with clinical, demographic and microscopic features of the patients. Otherwise, podoplanin expression by malignant epithelial cells was predominantly strong and significantly associated with radiotherapy (p = 0.004), muscular invasion (p = 0.006) and lymph node involvement (p = 0.013). Strong moesin expression was considered an unfavorable prognostic factor for patients with oral squamous cell carcinomas, clinical stage II and III (p = 0.024). Conclusions These results suggested that strong moesin expression by malignant cells may help to determine patients with oral squamous cell carcinoma and poor prognosis.
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Affiliation(s)
- Francisco Bárbara Abreu Barros
- Department of Stomatology, Area of Pathology, Bauru School of Dentistry, University of São Paulo, Alameda Octávio Pinheiro Brisolla, 9-75, Bauru, São Paulo, 17012-901, Brazil
| | - Agnes Assao
- Department of Stomatology, Area of Pathology, Bauru School of Dentistry, University of São Paulo, Alameda Octávio Pinheiro Brisolla, 9-75, Bauru, São Paulo, 17012-901, Brazil
| | - Natália Galvão Garcia
- Department of Stomatology, Area of Pathology, Bauru School of Dentistry, University of São Paulo, Alameda Octávio Pinheiro Brisolla, 9-75, Bauru, São Paulo, 17012-901, Brazil
| | - Suely Nonogaki
- Adolfo Lutz Institute, Pathology Division, São Paulo, Brazil
| | - André Lopes Carvalho
- Fundação Pio XII Institution - Cancer Hospital of Barretos, Barretos, São Paulo, Brazil
| | | | - Luiz Paulo Kowalski
- Department of Head and Neck Surgery and Otorhinolaringology, A.C.Camargo Cancer Center Hospital, São Paulo, Brazil
| | - Denise Tostes Oliveira
- Department of Stomatology, Area of Pathology, Bauru School of Dentistry, University of São Paulo, Alameda Octávio Pinheiro Brisolla, 9-75, Bauru, São Paulo, 17012-901, Brazil.
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14
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Sharma A, Boaz K, Natarajan S. Understanding patterns of invasion: a novel approach to assessment of podoplanin expression in the prediction of lymph node metastasis in oral squamous cell carcinoma. Histopathology 2017; 72:672-678. [DOI: 10.1111/his.13416] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 08/09/2017] [Accepted: 10/08/2017] [Indexed: 12/28/2022]
Affiliation(s)
- Ankita Sharma
- Department of Oral Pathology and Microbiology; Manipal College of Dental Sciences, Mangalore; Manipal University; Karnataka India
| | - Karen Boaz
- Department of Oral Pathology and Microbiology; Manipal College of Dental Sciences, Mangalore; Manipal University; Karnataka India
| | - Srikant Natarajan
- Department of Oral Pathology and Microbiology; Manipal College of Dental Sciences, Mangalore; Manipal University; Karnataka India
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15
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A G D, Janardanan-Nair B, B R V. Podoplanin expression in oral potentially malignant disorders and oral squamous cell carcinoma. J Clin Exp Dent 2017; 9:e1418-e1424. [PMID: 29410757 PMCID: PMC5794119 DOI: 10.4317/jced.54213] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2017] [Accepted: 10/23/2017] [Indexed: 11/17/2022] Open
Abstract
Background Podoplanin is a type I transmembrane sialomucin-like glycoprotein that is specifically expressed in lymphatic endothelial cells. Studies have shown that assessment of podoplanin expression in the epithelial cells can be used to predict the malignant transformation of potentially malignant disorders and the metastatic tendency of primary head and neck squamous cell carcinoma. The aim of our study was to compare the expression of podoplanin in oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma with that in normal buccal mucosa by immunohistochemical methods. Material and Methods Immunohistochemical expression of podoplanin was analyzed in 20 cases each of oral leukoplakia, oral submucous fibrosis, oral squamous cell carcinoma and normal buccal mucosa, with monoclonal antibody D2-40. The expression of podoplanin was graded from grade 0-4. Results There was a statistically significant upregulation of the grades of podoplanin expression in oral squamous cell carcinoma(100%), oral submucous fibrosis (90%) and oral leukoplakia (65%) when compared to that in normal mucosa(35%). Podoplanin expression increased with decrease in grades of differentiation in oral squamous cell carcinoma . Podoplanin expression in the samples of oral submucous fibrosis was higher than that in oral leukoplakia. Conclusions Evaluation of podoplanin expression in the epithelial cells of oral dysplastic lesions may provide valuable information to predict their risk of malignant transformation. Key words:Immunohistochemistry, Oral leukoplakia, Oral submucous fibrosis, Podoplanin, Squamous cell carcinoma.
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Affiliation(s)
- Deepa A G
- Assistant Professor, Department of Oral and Maxillofacial Pathology , Sree Mookambika Institute of Dental Sciences, Kulasekharam, Tamil Nadu, India
| | - Bindu Janardanan-Nair
- Consultant oral pathologist, Dr. Vivek's Dental Clinic, Vazhuthacaud, Trivandrum, Kerala, India
| | - Varun B R
- Associate Professor, Department of Oral and Maxillofacial Pathology PMS College of Dental Science and Research, Thiruvananthapuram, Kerala, India
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16
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Simonetti O, Lucarini G, Rubini C, Zizzi A, Aspriello SD, Di Primio R, Offidani AM. Correlation between immunohistochemical staining of CEACAM1 and clinicopathological findings in oral pre-neoplastic lesions and squamous cell carcinoma. Med Mol Morphol 2017; 51:41-47. [PMID: 28887602 DOI: 10.1007/s00795-017-0169-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 08/21/2017] [Indexed: 12/11/2022]
Abstract
Squamous cell carcinoma of the oral cavity represents the sixth most common cancer worldwide and it is often preceded by pre-neoplastic lesions. Sometimes it is still difficult for pathologists to make objective differential diagnoses only on histological characteristics. Tumorigenesis is accompanied by altered expression of cell adhesion molecules, like carcinoembryonic antigen cell adhesion molecule (CEACAM)1. We wanted to investigative CEACAM1 in oral dysplastic lesions, carcinoma in situ (CIS) and oral squamous cell carcinoma (OSCC). We examined immunohistochemical CEACAM1 expression in 50 OSCC, 30 oral CIS and 40 pre-neoplastic lesions and assessed its correlation with clinical and pathological parameters. CEACAM1 was not expressed in normal mucosa, significantly expressed in CIS while it was negative in all the dysplastic lesions. In OSCC, high CEACAM1 expression was associated with tumor grade and inversely correlated with both overall and disease-specific 5-year survival. We showed that CEACAM1 expression is very dynamic: absent in dysplastic lesions, up-regulated in CIS and OSCC. We suggest that CEACAM1 could be a prognostic marker of OSCC and oral CIS. Our most important finding was that it could help pathologists diagnosing oral carcinoma in situ.
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Affiliation(s)
- Oriana Simonetti
- Department of Dermatology, Polytechnic University of Marche, Torrette, Ancona, Italy
| | - Guendalina Lucarini
- Department of Clinic and Molecular Sciences, Histology, Polytechnic University of Marche, Via Tronto 10/a, Torrette, 60020, Ancona, Italy.
| | - Corrado Rubini
- Department of Biomedical Sciences and Public Health, Section of Pathologic Anatomy and Histopathology, Polytechnic University of Marche, Torrette, Ancona, Italy
| | - Antonio Zizzi
- Department of Biomedical Sciences and Public Health, Section of Pathologic Anatomy and Histopathology, Polytechnic University of Marche, Torrette, Ancona, Italy
| | | | - Roberto Di Primio
- Department of Clinic and Molecular Sciences, Histology, Polytechnic University of Marche, Via Tronto 10/a, Torrette, 60020, Ancona, Italy
| | - Anna Maria Offidani
- Department of Dermatology, Polytechnic University of Marche, Torrette, Ancona, Italy
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17
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Ikeda T, Seki S, Fujiwara M, Matsuura M, Ozaki-Honda Y, Fujita S, Ikeda H, Umeda M, Asahina I. Low-risk population among patients with tumor-node-metastasis stage III/IV oral squamous cell carcinoma. Oncol Lett 2017; 14:3711-3716. [PMID: 28927136 DOI: 10.3892/ol.2017.6575] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Accepted: 04/16/2017] [Indexed: 01/27/2023] Open
Abstract
A novel system auxiliary to the Union for International Cancer Control classification may allow the prognosis of patients with malignant tumors at similar stages to be predicted, as currently this is challenging. The present study generated a novel system to predict populations at low risk among patients with stage III/IV oral squamous cell carcinoma (OSCC). A total of 41 patients who were diagnosed at stages III/IV OSCC and underwent surgical tumor resection were analyzed. Band-like or follicular lymphocyte infiltration, intraepithelial micro-abscess formation and natural killer (NK) cell infiltration were histopathologically evaluated. Cox's proportional hazards regression model was used to identify prognostic factors, and a set of factors was selected from a combination of those prognostic factors to create a logic covariate model. A logic regression analysis for 41 patients with OSCC revealed that the presence of intraepithelial micro-abscesses and a lower density of NK cells were significantly associated with a favorable prognosis among patients with stage III/IV OSCC. These results suggested that the host innate immune responses, including neutrophil and NK cell infiltrations, are useful for prognostic prediction in patients with advanced malignant tumors.
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Affiliation(s)
- Tohru Ikeda
- Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
| | - Sachiko Seki
- Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan
| | - Mutsunori Fujiwara
- Department of Clinical Pathology, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan
| | - Masaaki Matsuura
- Graduate School of Public Health, Teikyo University, Tokyo 173-8605, Japan
| | - Yuu Ozaki-Honda
- Department of Clinical Physiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan
| | - Shuichi Fujita
- Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan
| | | | - Masahiro Umeda
- Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan
| | - Izumi Asahina
- Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan
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18
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Barbosa NG, Souza LB, Nonaka CFW, Silveira EJD. Evaluation of hypoxia, angiogenesis, and lymphangiogenesis in actinic cheilitis. Int J Dermatol 2017; 55:e573-e578. [PMID: 27420649 DOI: 10.1111/ijd.13365] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Revised: 02/14/2016] [Accepted: 04/07/2016] [Indexed: 01/08/2023]
Abstract
BACKGROUND Actinic cheilitis is a potentially malignant condition caused mainly by chronic sun exposure. Here we aim to evaluate the role of hypoxia, angiogenesis, and lymphatic density in the clinical and morphological progression of a series of cases of actinic cheilitis. MATERIALS AND METHODS Immunohistochemistry was used to evaluate positivity to hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF)-C, and D2-40 in 40 cases of actinic cheilitis of the lower lip. RESULTS The cases studied exhibited variable degrees of positivity to the markers. The median number of lymphatic vessels was 3.2, 2.4, and 3.0 in lesions showing no epithelial dysplasia (NED) and with mild (MED) and moderate (MOED) epithelial dysplasia, respectively. The median VEGF-C positivity index was 82.44% (NED), 92.74% (MED), and 82.83% (MOED), and the median HIF-1α positivity index was 11.57% (NED), 5.26% (MED), and 13.55% (MOED). No significant differences in lymphatic density or median VEGF-C and HIF-1α positivity indices were observed between histological grades or clinical presentations of actinic cheilitis (P > 0.05). CONCLUSIONS Although representing early events in lip carcinogenesis, the present results suggest that hypoxia, angiogenesis, and lymphangiogenesis do not influence the morphological or clinical progression of actinic cheilitis.
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Affiliation(s)
- Natália G Barbosa
- Oral Pathology Post-Graduate Program, Federal University of Rio Grande do Norte, Natal, Brazil.
| | - Lélia B Souza
- Oral Pathology Post-Graduate Program, Federal University of Rio Grande do Norte, Natal, Brazil
| | - Cassiano F W Nonaka
- Department of Dentistry, State University of Paraiba, Campina Grande, Brazil
| | - Ericka J D Silveira
- Oral Pathology Post-Graduate Program, Federal University of Rio Grande do Norte, Natal, Brazil
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19
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Proteomic and histopathological characterization of the interface between oral squamous cell carcinoma invasion fronts and non-cancerous epithelia. Exp Mol Pathol 2017; 102:327-336. [DOI: 10.1016/j.yexmp.2017.02.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 02/23/2017] [Indexed: 11/21/2022]
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20
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Hara H, Misawa T, Ishii E, Nakagawa M, Koshiishi S, Amemiya K, Oyama T, Tominaga K, Cheng J, Tanaka A, Saku T. Differential diagnosis of well-differentiated squamous cell carcinoma from non-neoplastic oral mucosal lesions: New cytopathologic evaluation method dependent on keratinization-related parameters but not nuclear atypism. Diagn Cytopathol 2017; 45:406-417. [PMID: 28205345 DOI: 10.1002/dc.23685] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 01/21/2017] [Accepted: 01/24/2017] [Indexed: 12/31/2022]
Abstract
BACKGROUND The cytology of oral squamous cell carcinoma (SCC) is challenging because oral SCC cells tend to be well differentiated and lack nuclear atypia, often resulting in a false negative diagnosis. The purpose of this study was to establish practical cytological parameters specific to oral SCCs. METHODS We reviewed 123 cases of malignancy and 53 of non-neoplastic lesions of the oral mucosa, which had been diagnosed using both cytology and histopathology specimens. From those, we selected 12 SCC and 4 CIS cases that had initially been categorized as NILM to ASC-H with the Bethesda system, as well as 4 non-neoplastic samples categorized as LSIL or ASC-H as controls, and compared their characteristic findings. After careful examinations, we highlighted five cytological parameters, as described in Results. Those 20 cytology samples were then reevaluated by 4 independent examiners using the Bethesda system as well as the 5 parameters. RESULTS Five cytological features, (i) concentric arrangement of orangeophilic cells (indicating keratin pearls), (ii) large number of orangeophilic cells, (iii) bizarre-shaped orangeophilic cells without nuclear atypia, (iv) keratoglobules, and (v) uneven filamentous cytoplasm, were found to be significant parameters. All malignant cases contained at least one of those parameters, while none were observed in the four non-neoplastic cases with nuclear atypia. In reevaluations, the Bethesda system did not help the screeners distinguish oral SCCs from non-neoplastic lesions, while use of the five parameters enabled them to make a diagnosis of SCC. CONCLUSION Recognition of the present five parameters is useful for oral SCC cytology. Diagn. Cytopathol. 2017;45:406-417. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Hitoshi Hara
- Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan
| | - Tsuneo Misawa
- Oral Surgery Division, Yamanashi Prefectural Central Hospital, Kofu, Japan
| | - Eri Ishii
- Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan
| | - Miki Nakagawa
- Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan
| | - Saki Koshiishi
- Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan
| | - Kenji Amemiya
- Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan
| | - Toshio Oyama
- Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan
| | - Kazuya Tominaga
- Department of Oral Pathology, Osaka Dental University, Hirakata, Japan
| | - Jun Cheng
- Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Akio Tanaka
- Department of Oral Pathology, Osaka Dental University, Hirakata, Japan
| | - Takashi Saku
- Department of Oral Pathology, Osaka Dental University, Hirakata, Japan.,Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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21
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Cañueto J, Cardeñoso-Álvarez E, Cosano-Quero A, Santos-Briz Á, Fernández-López E, Pérez-Losada J, Román-Curto C. The expression of podoplanin is associated with poor outcome in cutaneous squamous cell carcinoma. J Cutan Pathol 2016; 44:144-151. [DOI: 10.1111/cup.12859] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Revised: 10/28/2016] [Accepted: 11/01/2016] [Indexed: 12/13/2022]
Affiliation(s)
- Javier Cañueto
- Servicio de Dermatología; Hospital Universitario de Salamanca; Salamanca Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL); Hospital Universitario de Salamanca; Salamanca Spain
| | | | | | - Ángel Santos-Briz
- Servicio de Patología; Hospital Universitario de Salamanca; Salamanca Spain
| | - Emilia Fernández-López
- Servicio de Dermatología; Hospital Universitario de Salamanca; Salamanca Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL); Hospital Universitario de Salamanca; Salamanca Spain
| | - Jesús Pérez-Losada
- Instituto de Investigación Biomédica de Salamanca (IBSAL); Hospital Universitario de Salamanca; Salamanca Spain
- Instituto de Biología Molecular y Celular del Cáncer (IBMCC); Centro de investigación del Cáncer (CIC), Universidad de Salamanca/CSIC; Salamanca Spain
| | - Concepción Román-Curto
- Servicio de Dermatología; Hospital Universitario de Salamanca; Salamanca Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL); Hospital Universitario de Salamanca; Salamanca Spain
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22
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Podoplanin, ezrin, and Rho-A proteins may have joint participation in tumor invasion of lip cancer. Clin Oral Investig 2016; 21:1647-1657. [PMID: 27628318 DOI: 10.1007/s00784-016-1956-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 09/05/2016] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Podoplanin and ezrin connection through Rho-A phosphorylation have been suggested as part of the activation pathway, in the process of tumor invasion and cell movement in oral squamous cell carcinomas. OBJECTIVE The aim of this study was to evaluate the correlation among podoplanin, ezrin, and Rho-A immunoexpressions in 91 squamous cells carcinomas of the lower lip and their influence in patient's prognosis. MATERIAL AND METHODS The immunoexpressions of podoplanin, ezrin, and Rho-A were evaluated through a semi-quantitative score method, based on the capture of 10 microscopic fields at the front of tumor invasion. The association and correlation of these proteins with the clinicopathological features were verified by Fischer's exact test and Spearman's test. The prognostic values were analyzed by Kaplan-Meier method and log-rank test. RESULTS A statistically significant association between strong cytoplasmic podoplanin expression and alcohol (p = 0.024), loco-regional recurrences (p = 0.028), and lymph node metastasis (pN+) (p = 0.010) was found. The membranous (p = 0.000 and r = 0.384) and cytoplasmic (p = 0.000 and r = 0.344) podoplanin expression was statistically correlated with ezrin expression. Also, membranous podoplanin was significantly correlated with Rho-A expression (p = 0.006 and r = 0.282). The expressions of podoplanin, ezrin, and Rho-A were not significant prognostic factors for patients with squamous cell carcinomas of the lower lip. CONCLUSIONS Therefore, our results confirm a correlation among podoplanin, ezrin, and Rho-A expressions in squamous cell carcinoma of the lip suggesting a cooperative participation of these proteins in cell movement and invasion. CLINICAL RELEVANCE Furthermore, strong cytoplasmic podoplanin expression could be helpful to identify patients with squamous cell carcinoma of the lip and lower risk of loco-regional recurrences.
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23
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High relative density of lymphatic vessels predicts poor survival in tongue squamous cell carcinoma. Eur Arch Otorhinolaryngol 2016; 273:4515-4524. [DOI: 10.1007/s00405-016-4150-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Accepted: 06/14/2016] [Indexed: 01/28/2023]
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24
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Gao X, Ma L, Zhou Z, Jian X, Liu W. Podoplanin Expression Is Correlated With the Progression of Chronic Discoid Lupus Erythematosus to Lip Squamous Cell Carcinoma. Int J Surg Pathol 2016; 24:595-9. [PMID: 27240861 DOI: 10.1177/1066896916652220] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Chronic lip discoid lupus erythematosus (DLE) is a potentially malignant disorder that can develop into lip squamous cell carcinoma (LSCC). Podoplanin is a specific marker for lymphatic endothelial cells and plays a role in cancer progression. The objective of this study was to determine the immunoexpression of podoplanin in samples of patients with DLE and its correlation with the risk of progression to LSCC. In a retrospective study, podoplanin expression was determined using immunohistochemistry in samples from 52 patients with DLE, including 44 patients with untransformed DLE and 8 patients with malignant transformed DLE. Ten samples of normal oral mucosa and 10 samples of LSCC were used as normal and cancer controls, respectively. The results showed that podoplanin expression was observed in 12 of 44 (27.3%) patients with untransformed DLE and in 7 of 8 (87.5%) patients with transformed DLE (P = .002). Podoplanin was not expressed in normal oral mucosa, but it was overexpressed in all of the 10 patients with LSCC. Regression analysis revealed that podoplanin expression was significantly associated with an 18.67-fold increase in the risk of malignant progression (95% confidence interval = 2.07-168.10; P = .009). In summary, podoplanin expression is significantly associated with malignant transformation of DLE into LSCC. Thus, podoplanin expression may identify a subgroup with a high risk of malignant progression of DLE.
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Affiliation(s)
- Xing Gao
- XiangYa Hospital, Central South University, Changsha, Hunan, China
| | - Liwei Ma
- Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zengtong Zhou
- Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xinchun Jian
- XiangYa Hospital, Central South University, Changsha, Hunan, China
| | - Wei Liu
- Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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25
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Monteiro LS, Delgado ML, Ricardo S, do Amaral B, Salazar F, Pacheco JJ, Lopes CA, Bousbaa H, Warnakulasuryia S. Prognostic significance of CD44v6, p63, podoplanin and MMP-9 in oral squamous cell carcinomas. Oral Dis 2016; 22:303-12. [PMID: 26788715 DOI: 10.1111/odi.12442] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2015] [Revised: 12/20/2015] [Accepted: 01/11/2016] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To analyse the expression of the CD44v6, p63, podoplanin and MMP-9, and their prognostic significance in patients with oral squamous cell carcinomas (OSCC). MATERIAL AND METHODS Immunohistochemistry technique was performed on 60 OSCC for detection of CD44v6, p63, podoplanin and MMP-9 proteins. Extent and intensity of staining were evaluated in tumour cells and were compared with patients' clinical-pathological characteristics and survival. RESULTS CD44v6 expression was detected at the membrane of tumour cells of 94% cases. Nuclear expression of p63 protein was present in 96.5%. Podoplanin was observed at the membrane of tumour cells of 94% cases. MMP-9 was found in the cytoplasm of tumour cells in 83.7% cases. A high level of expression (67%-89%) in all four proteins was noted. Podoplanin was associated with the expression of MMP-9 (P = 0.010) and both were associated with lymph node metastasis (P = 0.011 and P = 0.018, respectively). Co-expression of podoplanin/MMP-9 was an adverse independent prognostic factor for cancer-specific survival (P = 0.008) and recurrence-free survival (P = 0.042). CONCLUSION Podoplanin and MMP-9 together could contribute to tumour progression and dissemination of OSCC. Their combined overexpression showed an adverse effect on survival, suggesting that they could be regarded as important prognostic biomarkers in OSCC.
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Affiliation(s)
- L S Monteiro
- CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS), IUCS - Instituto Universitário de Ciências da Saúde, Gandra, Portugal.,Medicine and Oral Surgery Department, Instituto Universitário de Ciências da Saúde, Gandra, Portugal
| | - M L Delgado
- CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS), IUCS - Instituto Universitário de Ciências da Saúde, Gandra, Portugal
| | - S Ricardo
- IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.,Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,Faculty of Medicine, University of Porto, Porto, Portugal
| | - B do Amaral
- CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS), IUCS - Instituto Universitário de Ciências da Saúde, Gandra, Portugal.,Medicine and Oral Surgery Department, Instituto Universitário de Ciências da Saúde, Gandra, Portugal.,Stomatology Department, Hospital de Santo António, Oporto Hospitalar Centre, Porto, Portugal
| | - F Salazar
- CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS), IUCS - Instituto Universitário de Ciências da Saúde, Gandra, Portugal.,Medicine and Oral Surgery Department, Instituto Universitário de Ciências da Saúde, Gandra, Portugal
| | - J J Pacheco
- CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS), IUCS - Instituto Universitário de Ciências da Saúde, Gandra, Portugal.,Medicine and Oral Surgery Department, Instituto Universitário de Ciências da Saúde, Gandra, Portugal
| | - C A Lopes
- Molecular Pathology and Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), Porto University, Porto, Portugal
| | - H Bousbaa
- CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS), IUCS - Instituto Universitário de Ciências da Saúde, Gandra, Portugal.,Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Porto, Portugal
| | - S Warnakulasuryia
- Oral Medicine, The WHO Collaborating Centre for Oral Cancer, King's College, London, UK
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Hasegawa M, Cheng J, Maruyama S, Yamazaki M, Abé T, Babkair H, Saito C, Saku T. Differential immunohistochemical expression profiles of perlecan-binding growth factors in epithelial dysplasia, carcinoma in situ, and squamous cell carcinoma of the oral mucosa. Pathol Res Pract 2016; 212:426-36. [PMID: 26965914 DOI: 10.1016/j.prp.2016.02.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 01/15/2016] [Accepted: 02/14/2016] [Indexed: 01/18/2023]
Abstract
The intercellular deposit of perlecan, a basement-membrane type heparan sulfate proteoglycan, is considered to function as a growth factor reservoir and is enhanced in oral epithelial dysplasia and carcinoma in situ (CIS). However, it remains unknown which types of growth factors function in these perlecan-enriched epithelial conditions. The aim of this study was to determine immunohistochemically which growth factors were associated with perlecan in normal oral epithelia and in different epithelial lesions from dysplasia and CIS to squamous cell carcinoma (SCC). Eighty-one surgical tissue specimens of oral SCC containing different precancerous stages, along with ten of normal mucosa, were examined by immunohistochemistry for growth factors. In normal epithelia, perlecan and growth factors were not definitely expressed. In epithelial dysplasia, VEGF, SHH, KGF, Flt-1, and Flk-1were localized in the lower half of rete ridges (in concordance with perlecan, 33-100%), in which Ki-67 positive cells were densely packed. In CIS, perlecan and those growth factors/receptors were more strongly expressed in the cell proliferating zone (63-100%). In SCC, perlecan and KGF disappeared from carcinoma cells but emerged in the stromal space (65-100%), while VEGF, SHH, and VEGF receptors remained positive in SCC cells (0%). Immunofluorescence showed that the four growth factors were shown to be produced by three oral SCC cell lines and that their signals were partially overlapped with perlecan signals. The results indicate that perlecan and its binding growth factors are differentially expressed and function in specific manners before (dysplasia/CIS) and after (SCC) invasion of dysplasia/carcinoma cells.
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Affiliation(s)
- Mayumi Hasegawa
- Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Jun Cheng
- Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Satoshi Maruyama
- Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata, Japan
| | - Manabu Yamazaki
- Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Tatsuya Abé
- Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata, Japan
| | - Hamzah Babkair
- Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Chikara Saito
- Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Takashi Saku
- Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata, Japan.
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Al-Eryani K, Cheng J, Abé T, Maruyama S, Yamazaki M, Babkair H, Essa A, Saku T. Protease-activated receptor 2 modulates proliferation and invasion of oral squamous cell carcinoma cells. Hum Pathol 2015; 46:991-9. [DOI: 10.1016/j.humpath.2015.03.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2014] [Revised: 03/08/2015] [Accepted: 03/11/2015] [Indexed: 12/16/2022]
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28
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Tsuneki M, Madri JA, Saku T. Cell–extracellular matrix interactions in oral tumorigenesis: Roles of podoplanin and CD44 and modulation of Hippo pathway. J Oral Biosci 2015. [DOI: 10.1016/j.job.2015.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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29
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Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms. Oncotarget 2015; 6:9045-60. [PMID: 25826087 PMCID: PMC4496201 DOI: 10.18632/oncotarget.3515] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Accepted: 02/04/2015] [Indexed: 11/25/2022] Open
Abstract
Podoplanin (PDPN) is a unique transmembrane receptor that promotes tumor cell motility. Indeed, PDPN may serve as a chemotherapeutic target for primary and metastatic cancer cells, particularly oral squamous cell carcinoma (OSCC) cells that cause most oral cancers. Here, we studied how a monoclonal antibody (NZ-1) and lectin (MASL) that target PDPN affect human OSCC cell motility and viability. Both reagents inhibited the migration of PDPN expressing OSCC cells at nanomolar concentrations before inhibiting cell viability at micromolar concentrations. In addition, both reagents induced mitochondrial membrane permeability transition to kill OSCC cells that express PDPN by caspase independent nonapoptotic necrosis. Furthermore, MASL displayed a surprisingly robust ability to target PDPN on OSCC cells within minutes of exposure, and significantly inhibited human OSCC dissemination in zebrafish embryos. Moreover, we report that human OSCC cells formed tumors that expressed PDPN in mice, and induced PDPN expression in infiltrating host murine cancer associated fibroblasts. Taken together, these data suggest that antibodies and lectins may be utilized to combat OSCC and other cancers that express PDPN.
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30
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Mikami T, Maruyama S, Abé T, Kobayashi T, Yamazaki M, Funayama A, Shingaki S, Kobayashi T, Jun C, Saku T. Keratin 17 is co-expressed with 14-3-3 sigma in oral carcinoma in situ and squamous cell carcinoma and modulates cell proliferation and size but not cell migration. Virchows Arch 2015; 466:559-69. [DOI: 10.1007/s00428-015-1735-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 12/24/2014] [Accepted: 02/03/2015] [Indexed: 10/23/2022]
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31
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de Vicente JC, Santamarta TR, Rodrigo JP, García-Pedrero JM, Allonca E, Blanco-Lorenzo V. Expression of podoplanin in the invasion front of oral squamous cell carcinoma is not prognostic for survival. Virchows Arch 2015; 466:549-58. [PMID: 25726183 DOI: 10.1007/s00428-015-1746-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2014] [Revised: 01/15/2015] [Accepted: 02/17/2015] [Indexed: 01/25/2023]
Abstract
Podoplanin is involved in actin remodeling of the cytoskeleton of tumor cells and may promote tumor cell invasion by increasing cell motility and formation of filopodia-like membrane protrusions. Podoplanin is expressed in a variety of tumors, but its role in head and neck cancer, particularly in oral squamous cell carcinoma, remains unclear. We studied podoplanin expression by immunohistochemistry in 92 oral squamous cell carcinomas (OSCC) using a monoclonal antibody against an epitope of podoplanin (D2-40). In terms of the number of stained cells, 34 OSCC (38 %) had low podoplanin expression (less than 33 % of cells), 33 (36 %) showed moderate expression (between 34 and 66 % of cells), and 21 (22 %) showed high expression. The intensity of immunostaining was strong in 26 (28 %) cases, moderate in 36 (40 %), and weak or negative in the remaining 30 tumors (32 %). Immunohistochemical expression of podoplanin was associated with a tumor histological grade. A diffuse pattern of podoplanin expression significantly decreased in moderately differentiated (37 %) and poorly differentiated (20 %) carcinomas compared to well-differentiated (43 %) carcinomas. In addition, the focal expression of podoplanin in the invasion front of the tumor, without expression in the tumor center, was observed in 72 % of well-differentiated tumors, 27 % of moderate tumors, and 0 % of poorly differentiated tumors. Moreover, a trend was found toward an association of diffuse podoplanin staining with the development of second primary carcinomas (13 %), in contrast to its expression in the invasion front (3 %). No association was observed between podoplanin expression and nodal metastasis.
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Affiliation(s)
- Juan Carlos de Vicente
- Department of Oral and Maxillofacial Surgery, Hospital Universitario Central de Asturias (HUCA), C/Carretera de Rubín, s/n, 33011, Oviedo, Asturias, Spain,
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32
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de Sousa EA, Lourenço SV, de Moraes FPP, Vartanian JG, Gonçalves-Filho J, Kowalski LP, Soares FA, Coutinho-Camillo CM. Head and neck squamous cell carcinoma lymphatic spread and survival: Relevance of vascular endothelial growth factor family for tumor evaluation. Head Neck 2014; 37:1410-6. [PMID: 24824527 DOI: 10.1002/hed.23765] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Revised: 03/14/2014] [Accepted: 05/10/2014] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Head and neck squamous cell carcinoma (HNSCC) is primarily a locoregional disease in which the cervical lymph nodes are the chief site of metastasis. The purpose of this study was to examine the relationship between lymphangiogenesis and clinicopathological aspects of HNSCC and its metastasis. METHODS Fifty-two patients with HNSCC and metastatic lymph nodes from 21 of these subjects were analyzed by immunohistochemistry. RESULTS The HNSCC samples were predominantly negative for vascular endothelial growth factor (VEGF)-C, VEGF-D, and vascular endothelial growth factor receptor (VEGFR)3. There was an association between the density of lymph vessels (measured by D2-40 staining) in the lymph nodes and advanced-stage tumors. There was no link between the expression of these proteins and survival rates. CONCLUSION Although lymphatic spread is a significant event in the progression of HNSCC, the expression of VEGF-C, VEGF-D, and VEGFR3 does not correlate with clinicopathological characteristics, suggesting that other signaling pathways mediate lymphangiogenesis in HNSCC.
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Affiliation(s)
| | | | | | - José Guilherme Vartanian
- Department of Head and Neck Surgery and Otorhinolaryngology, AC Camargo Cancer Center, São Paulo, Brazil
| | - João Gonçalves-Filho
- Department of Head and Neck Surgery and Otorhinolaryngology, AC Camargo Cancer Center, São Paulo, Brazil
| | - Luiz Paulo Kowalski
- Department of Head and Neck Surgery and Otorhinolaryngology, AC Camargo Cancer Center, São Paulo, Brazil
| | - Fernando Augusto Soares
- Department of Pathology, AC Camargo Cancer Center, São Paulo, Brazil.,Department of General Pathology, Dental School, University of São Paulo, Brazil
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33
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Podoplanin—a novel marker in oral carcinogenesis. Tumour Biol 2014; 35:8407-13. [DOI: 10.1007/s13277-014-2266-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2014] [Accepted: 06/19/2014] [Indexed: 02/04/2023] Open
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34
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Intraoperative assessment of surgical margins of oral squamous cell carcinoma using frozen sections: a practical clinicopathological management for recurrences. BIOMED RESEARCH INTERNATIONAL 2014; 2014:823968. [PMID: 25050372 PMCID: PMC4094714 DOI: 10.1155/2014/823968] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 06/03/2014] [Indexed: 01/23/2023]
Abstract
Background. Local recurrence remains a challenging clinical issue for the treatment of oral squamous cell carcinoma (SCC). We analyzed retrospectively how effective the frozen section technique (FS) was against recurrences of oral SCC. Methods. We screened 343 surgical samples from 236 patients who had oral SCC, carcinoma in situ (CIS), or epithelial dysplasia, and we followed up their clinical outcomes for at least 5 years. Histopathological states of surgical margins were compared between FS and surgical materials in relapse and relapse-free groups, respectively. Results. Among the 236 patients, 191 were classified into the relapse-free group, and 45 into the relapse group. FS was more frequently performed in the relapse-free group (128/191) than in the relapse group (83/152). Histopathologically, moderate dysplasia or CIS (borderline malignancies) and SCC were recognized in 55 samples of the relapse-free group and in 57 of the relapse group. For those surgical margins with borderline malignancies, additional incisions were performed in 38 of the 55 relapse-free cases, which reduced to 20 from the 38 margins with borderline malignancies (47.4% reduction), and in 39 of the 57 relapse cases, which reduced to only 3 of 39 (7.7% reduction). Conclusions. The intraoperative assessment of surgical margins by FS is essential in preventing recurrences of oral mucosal malignancies.
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35
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Kim HS, Park YW. Metastasis via Peritumoral Lymphatic Dilation in Oral Squamous Cell Carcinoma. Maxillofac Plast Reconstr Surg 2014; 36:85-93. [PMID: 27489817 PMCID: PMC4281901 DOI: 10.14402/jkamprs.2014.36.3.85] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2014] [Revised: 05/07/2014] [Accepted: 05/26/2014] [Indexed: 11/17/2022] Open
Abstract
PURPOSE Nodal metastasis is the main prognostic factor in the patients with oral squamous cell carcinoma (OSCC). We investigated the association between tumor-associated lymphatics and OSCC characteristics. METHODS Thirty-four specimens were used for the immunohistochemical staining with the antibody for vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, phosphorylated VEGFR-3, D2-40, and matrix metallproteinases (MMPs). We observed the distribution of the lymphangiogenic factors and quantified the degree of expression. We determined lymphatic vessel density (LVD) and lymphatic vessel dilatation with D2-40 immunostaining. We assessed the association of LVD or lymphatic vessel dilatation with tumor progression or tumor differentiation. RESULTS OSCC cells expressed lymphangiogenic ligands. Lymphangiogenic receptor, VEGFR-3, was expressed and activated in some tumor cells as well as in tumor-associated endothelial cells. LVD was not associated with tumor size or nodal status, but lymphatic vessel dilatation was higher in tumors with nodal metastasis, and also higher in poorly differentiated tumors. In stromal area of OSCC, MMP-1 and MMP-10 were up-regulated and the basement membrane of tumor-associated endothelial cells was destroyed by these collagenases. CONCLUSION In the primary tumors with nodal metastasis, especially in poorly differentiated OSCC, tumor cells invaded the dilated lymphatic vessels via ruptured sites. MMP-1 and MMP-10 are important in the lysis of the glycocalyx inside the tumor-associated lymphatic endothelial cells.
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Affiliation(s)
- Han-Seok Kim
- Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University
| | - Young-Wook Park
- Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University
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36
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Maruyama S, Shimazu Y, Kudo T, Sato K, Yamazaki M, Abé T, Babkair H, Cheng J, Aoba T, Saku T. Three-dimensional visualization of perlecan-rich neoplastic stroma induced concurrently with the invasion of oral squamous cell carcinoma. J Oral Pathol Med 2014; 43:627-36. [PMID: 24697873 DOI: 10.1111/jop.12184] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND We have demonstrated the induction of perlecan-rich stroma of oral squamous cell carcinoma (SCC) on and after its start of invasion. However, it remains unknown how such a neoplastic stroma is actually arranged in tumor tissues. METHODS To this end, tissue microarray samples, in which keratin and perlecan were contrastively labeled by immunohistochemistry, were three-dimensionally analyzed using digital images and image analysis software to demonstrate the relationship between SCC foci and the perlecan-positive stromal space or that between carcinoma in situ (CIS) and invasive SCC foci. RESULTS The three-dimensional (3D) reconstruction demonstrated three kinds of perlecan profiles for inside (I) and outside (O) areas of the carcinoma cell focus: mode 1, I(+)/O(-) ; mode 2, I(+)/O(+) ; and mode 3, I(-)/O(+). Mode 1 was seen in CIS as well as SCC tumor massifs in the surface part. Mode 2 was seen in small SCC foci, which seemed isolated in 2D sections but were mostly continuous with the tumor massif in 3D reconstructions. Mode 3 was limited to small SCC foci, which were truly segregated from the tumor massif. CONCLUSIONS The results indicated that the 2D SCC focus isolation could not be regarded as invasion but that the SCC foci surrounded by perlecan-positive stroma (modes 2 and 3) could be regarded as a more objective measure for invasion of SCC. This is the first 3D tissue-level demonstration of the neoplastic stroma space induced with oral SCC invasion, the presence of which we have predicted based on our previous 2D and tissue culture evidence.
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Affiliation(s)
- Satoshi Maruyama
- Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata, Japan
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Seki S, Fujiwara M, Matsuura M, Fujita S, Ikeda H, Umeda M, Asahina I, Ikeda T. Prognostic value of podoplanin expression in oral squamous cell carcinoma--a regression model auxiliary to UICC classification. Pathol Oncol Res 2013; 20:521-8. [PMID: 24281769 DOI: 10.1007/s12253-013-9723-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Accepted: 11/05/2013] [Indexed: 12/17/2022]
Abstract
Podoplanin, a type I transmembrane glycoprotein with an effect of platelet aggregation, has been reported to be one of the possible prognostic factors of oral squamous cell carcinoma (OSCC). However, the biological significance of podoplanin is largely unclear. The aim of this study was to develop a practical model for the prediction of prognosis using the grade of podoplanin expression, and also to evaluate the biological function of podoplanin. Eighty-two specimens of patients with previously untreated OSCC, who underwent either biopsy or surgery, were histopathologically and immunohistochemically analyzed. These 82 cases were composed of 66 well-differentiated, 10 moderately differentiated and 6 poorly differentiated OSCC. Podoplanin was successfully immunostained in 78 specimens, and was detected in most cases, but the frequency of positive cells varied. The prognosis of patients with more than 50 % podoplanin-positive tumor cells was significantly poorer than that of the other patients. Multivariate hazards regression analysis suggested that a linear combination of covariates, OSCC patients with more or less than 50 % podoplanin expression, age of more or less than 70 years old, mode of invasion and T3, T4 or T2 versus T1 of the UICC T-stage classification was the most effective model for evaluating the prognosis of OSCC patients. Additionally, podoplanin expression had a significant relationship to UICC clinical stage and the expression of Ki-67. An effective regression model using podoplanin expression was developed for evaluating the prognosis of OSCC and the biological significance of podoplanin was suggested to be associated with the growth and/or progression of OSCC.
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Affiliation(s)
- Sachiko Seki
- Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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38
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Ebp1 activates podoplanin expression and contributes to oral tumorigenesis. Oncogene 2013; 33:3839-50. [DOI: 10.1038/onc.2013.354] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2013] [Revised: 06/18/2013] [Accepted: 07/15/2013] [Indexed: 12/15/2022]
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39
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Podoplanin-mediated cell adhesion through extracellular matrix in oral squamous cell carcinoma. J Transl Med 2013; 93:921-32. [PMID: 23817087 DOI: 10.1038/labinvest.2013.86] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Revised: 04/29/2013] [Accepted: 05/27/2013] [Indexed: 11/08/2022] Open
Abstract
Podoplanin (PDPN), one of the representative mucin-like type-I transmembrane glycoproteins specific to lymphatic endothelial cells, is expressed in various cancers including squamous cell carcinoma (SCC). On the basis of our previous studies, we have developed the hypothesis that PDPN functions in association with the extracellular matrix (ECM) from the cell surface side. The aim of this study was to elucidate the molecular role of PDPN in terms of cell adhesion, proliferation, and migration in oral SCC cells. Forty-four surgical specimens of oral SCC were used for immunohistochemistry for PDPN, and the expression profiles were correlated with their clinicopathological properties. Using ZK-1, a human oral SCC cell system, and five other cell systems, we examined PDPN expression levels by immunofluorescence, western blotting, and real-time PCR. The effects of transient PDPN knockdown by siRNA in ZK-1 were determined for cellular functions in terms of cell proliferation, adhesion, migration, and invasion in association with CD44 and hyaluronan. Cases without PDPN-positive cells were histopathologically classified as less-differentiated SCC, and SCC cells without PDPN more frequently invaded lymphatics. Adhesive properties of ZK-1 were significantly inhibited by siRNA, and PDPN was shown to collaborate with CD44 in cell adhesion to tether SCC cells with hyaluronan-rich ECM of the narrow intercellular space as well as with the stromal ECM. There was no siRNA effect in migration. We have demonstrated the primary function of PDPN in cell adhesion to ECM, which is to secondarily promote oral SCC cell proliferation.
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40
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Intercellular contact augments epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3)-activation which increases podoplanin-expression in order to promote squamous cell carcinoma motility. Cell Signal 2013; 25:760-5. [DOI: 10.1016/j.cellsig.2012.12.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2012] [Accepted: 12/18/2012] [Indexed: 01/13/2023]
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41
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Tsuneki M, Maruyama S, Yamazaki M, Xu B, Essa A, Abé T, Babkair H, Cheng J, Yamamoto T, Saku T. Extracellular heat shock protein A9 is a novel interaction partner of podoplanin in oral squamous cell carcinoma cells. Biochem Biophys Res Commun 2013; 434:124-30. [PMID: 23541579 DOI: 10.1016/j.bbrc.2013.03.057] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2013] [Accepted: 03/13/2013] [Indexed: 01/28/2023]
Abstract
In previous studies, we have shown several lines of evidence that podoplanin (PDPN) plays an important role in cell adhesion via its association with extracellular components in neoplastic conditions, though there has been no trial to search for PDPN-interaction molecules in the extracellular milieu. To screen for those molecules, we performed proteomics-based analysis using liquid chromatography-tandem mass spectrometry followed by co-immunoprecipitation for PDPN in ZK-1, an oral squamous cell carcinoma (SCC) cell system whose cell membrane molecules were cross-linked with each other in their extracellular compartments, and we identified heat shock protein (HSP) A9 as one of the extracellular PDPN bound molecules. Effects of transient PDPN knockdown by siRNA in ZK-1 were also comparatively examined for cellular behaviors in terms of HSPA9 expression and secretion. Finally, HSPA9 expression modes were immunohistochemically visualized in oral SCC tissue specimens. HSPA9 was secreted from ZK-1 cells, and the expression and secretion levels of HSPA9 gene and protein were well coordinated with those of PDPN. Immunohistochemically, HSPA9 and PDPN were co-localized in ZK-1 cells and oral SCC foci, especially in the peripheral zone. In conclusion, the results indicate that HSPA9 secreted by oral SCC cells interacts with PDPN on their cell surface in an autocrine manner and regulates their growth and invasiveness.
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Affiliation(s)
- Masayuki Tsuneki
- Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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Krishnan H, Ochoa-Alvarez JA, Shen Y, Nevel E, Lakshminarayanan M, Williams MC, Ramirez MI, Miller WT, Goldberg GS. Serines in the intracellular tail of podoplanin (PDPN) regulate cell motility. J Biol Chem 2013; 288:12215-21. [PMID: 23530051 DOI: 10.1074/jbc.c112.446823] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Podoplanin (PDPN) is a transmembrane receptor that affects the activities of Rho, ezrin, and other proteins to promote tumor cell motility, invasion, and metastasis. PDPN is found in many types of cancer and may serve as a tumor biomarker and chemotherapeutic target. The intracellular region of PDPN contains only two serines, and these are conserved in mammals including mice and humans. We generated cells from the embryos of homozygous null Pdpn knock-out mice to investigate the relevance of these serines to cell growth and migration on a clear (PDPN-free) background. We report here that one or both of these serines can be phosphorylated by PKA (protein kinase A). We also report that conversion of these serines to nonphosphorylatable alanine residues enhances cell migration, whereas their conversion to phosphomimetic aspartate residues decreases cell migration. These results indicate that PKA can phosphorylate PDPN to decrease cell migration. In addition, we report that PDPN expression in fibroblasts causes them to facilitate the motility and viability of neighboring melanoma cells in coculture. These findings shed new light on how PDPN promotes cell motility, its role in tumorigenesis, and its utility as a functionally relevant biomarker and chemotherapeutic target.
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Affiliation(s)
- Harini Krishnan
- Graduate School of Biomedical Sciences and Department of Molecular Biology, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey 08084, USA
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Cancer stem cell markers in head and neck squamous cell carcinoma. Stem Cells Int 2013; 2013:319489. [PMID: 23533441 PMCID: PMC3603684 DOI: 10.1155/2013/319489] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Accepted: 01/23/2013] [Indexed: 12/22/2022] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) is one of the world's top ten most common cancers. Current survival rates are poor with only 50% of patients expected to survive five years after diagnosis. The poor survival rate of HNSCC is partly attributable to the tendency for diagnosis at the late stage of the disease. One of the reasons for treatment failure is thought to be related to the presence of a subpopulation of cells within the tumour called cancer stem cells (CSCs). CSCs display stem cell-like characteristics that impart resistance to conventional treatment modalities and promote tumour initiation, progression, and metastasis. Specific markers for this population have been investigated in the hope of developing a deeper understanding of their role in the pathogenesis of HNSCC and elucidating novel therapeutic strategies.
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Podoplanin is a novel myoepithelial cell marker in pleomorphic adenoma and other salivary gland tumors with myoepithelial differentiation. Virchows Arch 2012; 462:297-305. [PMID: 23262786 DOI: 10.1007/s00428-012-1359-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2012] [Revised: 11/21/2012] [Accepted: 12/10/2012] [Indexed: 12/19/2022]
Abstract
The expression of podoplanin, one of the representative immunohistochemical markers for lymphatic endothelium, is upregulated in various kinds of cancers. Based on our previous studies, we have developed a hypothesis that podoplanin plays a role in cell adhesion via its association with extracellular matrix (ECM). Since salivary pleomorphic adenoma is histologically characterized by its ECM-enriched stroma, we firstly wanted to explore the expression modes of podoplanin in pleomorphic adenoma and related salivary tumors by immunohistochemistry. In normal salivary gland, podoplanin was specifically localized in myoepithelial cells, which were also positively labeled by antibodies against P63, of the intercalated duct as well as acini. In pleomorphic adenoma, podoplanin was colocalized with P63 and CD44 in basal cells of glandular structures as well as in stellate/spindle cells in myxochondroid matrices, where perlecan and hyaluronic acid were enriched. The expression of podoplanin was confirmed at both protein and mRNA levels in pleomorphic adenoma cell systems (SM-AP1 and SM-AP4) by using immunofluorescence, western blotting, and reverse transcription polymerase chain reaction. Podoplanin was localized on the cell border as well as in the external periphery of the cells. Moreover, podoplanin expression was also confirmed in tumor cells with myoepithelial differentiation in myoepithelioma and intraductal papilloma. The results indicate that podoplanin can be regarded as a novel myoepithelial marker in salivary gland tumors and suggest that podoplanin's communication with ECM molecules is essential to phenotypic differentiation to myoepithelial cells.
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Kobayashi T, Maruyama S, Abé T, Cheng J, Takagi R, Saito C, Saku T. Keratin 10-positive orthokeratotic dysplasia: a new leucoplakia-type precancerous entity of the oral mucosa. Histopathology 2012; 61:910-20. [DOI: 10.1111/j.1365-2559.2012.04283.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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Feng JQ, Mi JG, Wu L, Ma LW, Shi LJ, Yang X, Liu W, Zhang CP, Zhou ZT. Expression of podoplanin and ABCG2 in oral erythroplakia correlate with oral cancer development. Oral Oncol 2012; 48:848-52. [PMID: 22525603 DOI: 10.1016/j.oraloncology.2012.03.015] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Revised: 03/12/2012] [Accepted: 03/17/2012] [Indexed: 12/29/2022]
Abstract
Oral erythroplakia (OE) is a notoriously aggressive oral premalignant lesion with a high tendency to oral cancer development, but it's biological behavior is largely unknown. The objective of the current study was to determine podoplanin and ABCG2 immunoexpression in OE and both correlation to malignant transformation of OE. In a retrospective follow-up study, the expression patterns of podoplanin and ABCG2 were determined using immunohistochemistry in samples from 34 patients with OE, including patients with untransformed lesions (n=17) and patients with malignant transformed lesions (n=17). Podoplanin and ABCG2 expression was observed in 15 (44.1%) and 21 (61.8%) of 34 patients, respectively. Multivariate analysis revealed that podoplanin and ABCG2 expression was associated with 6.31-fold (95% confidence interval [CI], 1.02-38.92; P=0.047) and 14.39-fold (95% CI, 2.02-102.29; P=0.008) increased the risk of transformation, respectively. Point prevalence analysis revealed that 90.9% (95% CI, 70.7-100) of the patient with both podoplanin and ABCG2 positivity developed oral cancer. Collectively, our data indicated that the expression patterns of podoplanin and ABCG2 in OE were associated with oral cancer development, suggesting that podoplanin and ABCG2 may be valuable predictors for evaluating oral cancer risk.
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Affiliation(s)
- Jin-Qiu Feng
- Department of Preventive Dentistry, Shanghai Municipal Hospital for Oral Health, Shanghai, China
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Toll A, Gimeno-Beltrán J, Ferrandiz-Pulido C, Masferrer E, Yébenes M, Jucglà A, Abal L, Martí RM, Sanmartín O, Baró T, Casado B, Gandarillas A, Barranco C, Costa I, Mojal S, García-Patos V, Pujol RM. D2-40 immunohistochemical overexpression in cutaneous squamous cell carcinomas: a marker of metastatic risk. J Am Acad Dermatol 2012; 67:1310-8. [PMID: 22521203 DOI: 10.1016/j.jaad.2012.03.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2011] [Revised: 03/06/2012] [Accepted: 03/08/2012] [Indexed: 01/05/2023]
Abstract
BACKGROUND Approximately 4% of cutaneous squamous cell carcinomas (cSCCs) develop lymphatic metastases. The value of lymphatic endothelial markers to enhance the detection of lymphatic tumor invasion in cSCC has not been assessed previously. OBJECTIVE We sought to evaluate the use of the antibody D2-40, a podoplanin immunohistochemical marker, to identify tumor lymph vessel invasion in cSCC and to assess its expression in tumor cells. METHODS This was a retrospective case-control study. A series of 101 cSCC, including 51 cases that developed lymphatic metastatic spread (metastasizing cSCC [MSCC]) and 50 cases that resolved definitely after surgical excision (non-MSCC) were included in the study. Lymph vessel invasion using D2-40 was evaluated on all primary biopsy specimens. The percentage of tumor cells showing D2-40 positivity and intensity scoring were recorded. All the immunohistochemical findings were correlated with the clinicopathological features. RESULTS Lymph vessel invasion was observed in 8% of non-MSCCs and in 25.5% of MSCCs (P = .031). D2-40 expression was significantly increased, both in intensity (odds ratio 4.42 for intensity ++/+++) and in area (odds ratio 2.29 for area >10%), in MSCC when compared with non-MSCC. Interestingly, almost half (49%) of the MSCC had moderate to intense D2-40 positivity compared with 16% of non-MSCC. D2-40 immunohistochemical expression was increased in tumors with an infiltrative pattern of extension. In the multivariate analysis, histologically poorly differentiated tumors, recurrent lesions, and cSCC showing D2-40 overexpression (in intensity) were significantly associated with lymphatic metastases development (odds ratios 15.67, 14.72, and 6.07, respectively). LIMITATIONS This was a retrospective study. CONCLUSION The expression of podoplanin associates with high metastatic risk in cSCC.
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Affiliation(s)
- Agustí Toll
- Department of Dermatology, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain.
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Intraepithelially entrapped blood vessels in oral carcinoma in-situ. Virchows Arch 2012; 460:473-80. [DOI: 10.1007/s00428-012-1224-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2011] [Revised: 12/26/2011] [Accepted: 01/30/2012] [Indexed: 01/14/2023]
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Kreppel M, Kreppel B, Drebber U, Wedemayer I, Rothamel D, Zöller JE, Scheer M. Podoplanin expression in oral leukoplakia: prognostic value and clinicopathological implications. Oral Dis 2012; 18:692-9. [DOI: 10.1111/j.1601-0825.2012.01927.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Agaimy A, Kirsche H, Semrau S, Iro H, Hartmann A. Cytokeratin-positive epithelioid angiosarcoma presenting in the tonsil: a diagnostic challenge. Hum Pathol 2012; 43:1142-7. [PMID: 22406364 DOI: 10.1016/j.humpath.2011.10.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2011] [Revised: 10/20/2011] [Accepted: 10/24/2011] [Indexed: 12/15/2022]
Abstract
Primary oral cavity sarcomas are exceedingly rare and may pose a great diagnostic challenge. A 71-year-old woman without history of malignancy or radiation to the head and neck presented with an antibiotic-refractory diffuse painful swelling of the right tonsil necessitating tonsillectomy. Histologic evaluation revealed subtotal replacement of the right tonsil by a high-grade epithelioid neoplasm displaying extensive ulceration, necrosis, and primitive vasoformation. Immunohistochemistry showed strong/diffuse expression of pancytokeratin antibodies KL-1 and Lu5, cytokeratin 8, cytokeratin 18, cytokeratin 19, vimentin, CD31, ERG, and Freund leukemia integration site 1 (FLI-1). High-molecular-weight cytokeratins (cytokeratin 5, 34β12), cytokeratin 7, cytokeratin 13, and cytokeratin 20 were not expressed. Within months, the patient underwent surgical resection of multiple bleeding intraoral and gastrointestinal metastases. She is currently alive with disease 9 months from diagnosis. To our knowledge, this case represents the first well-documented primary epithelioid angiosarcoma of the tonsil. The strong cytokeratin expression in epithelioid angiosarcomas represents a diagnostic pitfall. Thus, awareness of this rare and highly aggressive neoplasm is necessary for distinguishing it from poorly differentiated and acantholytic squamous cell carcinoma and diffuse large cell lymphoma.
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Affiliation(s)
- Abbas Agaimy
- Institute of Pathology, University Hospital, 91054 Erlangen, Germany.
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