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Li W, Huang L, Qi N, Zhang Q, Qin Z. Upregulation of CALD1 predicted a poor prognosis for platinum-treated ovarian cancer and revealed it as a potential therapeutic resistance target. BMC Genomics 2024; 25:183. [PMID: 38365611 PMCID: PMC10870461 DOI: 10.1186/s12864-024-10056-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 01/27/2024] [Indexed: 02/18/2024] Open
Abstract
BACKGROUND Ovarian cancer (OC) has the worst prognosis among gynecological malignancies, most of which are found to be in advanced stage. Cell reduction surgery based on platinum-based chemotherapy is the current standard of treatment for OC, but patients are prone to relapse and develop drug resistance. The objective of this study was to identify a specific molecular target responsible for platinum chemotherapy resistance in OC. RESULTS We screened the protein-coding gene Caldesmon (CALD1), expressed in cisplatin-resistant OC cells in vitro. The prognostic value of CALD1 was evaluated using survival curve analysis in OC patients treated with platinum therapy. The diagnostic value of CALD1 was verified by drawing a Receiver Operating Characteristic (ROC) curve using clinical samples from OC patients. This study analyzed data from various databases including Gene Expression Omnibus (GEO), Human Protein Atlas (HPA), The Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA), GEPIA 2, UALCAN, Kaplan-Meier (KM) plotter, LinkedOmics database, and String. Different expression genes (DEGs) between cisplatin-sensitive and cisplatin-resistant cells were acquired respectively from 5 different datasets of GEO. CALD1 was selected as a common gene from 5 groups DEGs. Online data analysis of HPA and CCLE showed that CALD1 was highly expressed in both normal ovarian tissue and OC. In TCGA database, high expression of CALD1 was associated with disease stage and venous invasion in OC. Patients with high CALD1 expression levels had a worse prognosis under platinum drug intervention, according to Kaplan-Meier (KM) plotter analysis. Analysis of clinical sample data from GEO showed that CALD1 had superior diagnostic value in distinguishing patients with platinum "resistant" and platinum "sensitive" (AUC = 0.816), as well as patients with worse progression-free survival (AUC = 0.741), and those with primary and omental metastases (AUC = 0.811) in ovarian tumor. At last, CYR61 was identified as a potential predictive molecule that may play an important role alongside CALD1 in the development of platinum resistance in OC. CONCLUSIONS CALD1, as a member of cytoskeletal protein, was associated with poor prognosis of platinum resistance in OC, and could be used as a target protein for mechanism study of platinum resistance in OC.
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Affiliation(s)
- Wei Li
- Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530002, China
| | - Limei Huang
- Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530002, China
| | - Nana Qi
- Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530002, China
| | - Qinle Zhang
- Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530002, China.
| | - Zailong Qin
- Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530002, China.
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Ozden SB, Simsekoglu MF, Sertbudak I, Demirdag C, Gurses I. Epithelioid malignant peripheral nerve sheath tumor of the bladder and concomitant urothelial carcinoma: A case report. World J Clin Cases 2024; 12:551-559. [PMID: 38322457 PMCID: PMC10841956 DOI: 10.12998/wjcc.v12.i3.551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 08/08/2023] [Accepted: 08/17/2023] [Indexed: 01/18/2024] Open
Abstract
BACKGROUND Epithelioid malignant peripheral nerve sheath tumor (EMPNST) of the bladder is a rare entity with devastating features. These tumors are thought to originate from malignant transformation of pre-existing schwannomas of pelvic autonomic nerve plexuses, and unlike the conventional malignant peripheral nerve sheath tumor (MPNST), are not associated with neurofibromatosis. The tumor has distinctive morphological, immunohistochemical and molecular features. Additionally, it tends to be more aggressive and have a higher mortality. This is the first case that presents with a synchronous urothelial carcinoma of the bladder and the epithelioid variant of MPNST in the literature. It's also the second reported case of EMPNST originating from the bladder wall. CASE SUMMARY In this case report, we present the detailed clinical course of a 71-year-old patient with EMPNST of the bladder alongside a literature review. CONCLUSION During the management of EMPNST cases, offering aggressive treatment modalities to the patient, such as radical cystectomy, is appropriate for the best chance to contain the disease, regardless of the tumor stage and the extent of local disease at initial diagnosis.
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Affiliation(s)
- Sami Berk Ozden
- Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine Department of Urology, Istanbul 34100, Fatih, Turkey
| | - Muhammed Fatih Simsekoglu
- Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine Department of Urology, Istanbul 34100, Fatih, Turkey
| | - Ipek Sertbudak
- Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine Department of Pathology, Istanbul 34100, Fatih, Turkey
| | - Cetin Demirdag
- Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine Department of Urology, Istanbul 34100, Fatih, Turkey
| | - Iclal Gurses
- Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine Department of Pathology, Istanbul 34100, Fatih, Turkey
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3
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Zeng SP, Sun YF, Ye JB, Zeng K, Li XB. Transurethral en bloc resection of a bladder perivascular epithelioid cell tumor (PEComa): a case report. BMC Urol 2023; 23:28. [PMID: 36864398 PMCID: PMC9983238 DOI: 10.1186/s12894-023-01198-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Accepted: 02/23/2023] [Indexed: 03/04/2023] Open
Abstract
BACKGROUND Perivascular epithelioid cell tumor (PEComa) is a mesenchymal tumor with distinct histologic and immunologic features. PEComas that originate in the bladder are extremely rare clinically, with only 35 cases reported in the English literature thus far. Here, we report a case of bladder PEComa resection by transurethral en bloc resection of bladder tumor (ERBT). CASE PRESENTATION A 66-year-old female with a history of poorly controlled type 2 diabetes with associated complications of frequent urinary tract infections presented to our hospital for a routine physical examination. Outpatient ultrasound examination revealed a strong echogenic mass of approximately 1.5 × 1.3 × 1.3 cm in size on the posterior wall of the bladder. The enhanced computed tomography and enhanced magnetic resonance imaging after admission both suggested a well-defined isolated nodular mass on the posterior wall of the bladder with significant enhancement on the enhanced scan. The tumor was successfully and completely resected by ERBT. Postoperative pathological examination and immunohistochemical results confirmed the mass was a bladder PEComa. No tumor recurrence was observed in the six-month postoperative follow-up. CONCLUSION Bladder PEComa is an extremely rare mesenchymal tumor of the urinary system. When imaging and cystoscopy reveal a nodular mass with an abundant blood supply in the bladder, PEComa should be included in the differential diagnosis of bladder tumors. Surgical resection is currently the primary option for the treatment of bladder PEComa. For a solitary, pedunculated, narrow-based, small-sized bladder PEComa, resection of the tumor by ERBT was a safe and feasible approach in our patient and may be considered for similar cases in the future.
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Affiliation(s)
- Shi-Ping Zeng
- grid.507975.9Department of Urology, Zigong First People’s Hospital, Zigong, China
| | - Yi-Fei Sun
- grid.412901.f0000 0004 1770 1022Neurological Disease Laboratory, West China Hospital of Sichuan University, Chengdu, China
| | - Jun-Bing Ye
- grid.507975.9Department of Urology, Zigong First People’s Hospital, Zigong, China
| | - Ke Zeng
- grid.507975.9Department of Urology, Zigong First People’s Hospital, Zigong, China
| | - Xiao-Bin Li
- Department of Urology, Zigong First People's Hospital, Zigong, China.
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4
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Kokura K, Watanabe J, Murata S, Uemura Y, Uegaki M, Shirahase T. A case of bladder perivascular epithelioid cell tumors. Urol Case Rep 2022; 45:102168. [PMID: 35991213 PMCID: PMC9386111 DOI: 10.1016/j.eucr.2022.102168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 07/04/2022] [Accepted: 07/16/2022] [Indexed: 11/02/2022] Open
Abstract
Perivascular epithelioid cell tumor (PEComa) was introduced in the WHO classification of bone and soft tissue tumors in 2002, and Bladder PEComa is very rare. A 60-year-old man underwent TURBT after CT and cystoscopy revealed a 2.5 cm tumor with a concave center on the posterior wall of the bladder. Pathological examination revealed a perivascular epithelioid cell tumor, which was diagnosed as primary bladder PEComa after systemic examination. We report a case of partial bladder resection for bladder PEComa, a type of mesenchymal tumor that does not originate from the bladder mucosa.
PEComa is a new classification introduced by WHO in 2002. PEComa generally have a benign course, but some may turn malignant. Partial bladder resection is considered for the curative treatment of bladder PEComa.
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Alnuaimi AR, Nair VA, Malhab LJB, Abu-Gharbieh E, Ranade AV, Pintus G, Hamad M, Busch H, Kirfel J, Hamoudi R, Abdel-Rahman WM. Emerging role of caldesmon in cancer: A potential biomarker for colorectal cancer and other cancers. World J Gastrointest Oncol 2022; 14:1637-1653. [PMID: 36187394 PMCID: PMC9516648 DOI: 10.4251/wjgo.v14.i9.1637] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/05/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023] Open
Abstract
Colorectal cancer (CRC) is a devastating disease, mainly because of metastasis. As a result, there is a need to better understand the molecular basis of invasion and metastasis and to identify new biomarkers and therapeutic targets to aid in managing these tumors. The actin cytoskeleton and actin-binding proteins are known to play an important role in the process of cancer metastasis because they control and execute essential steps in cell motility and contractility as well as cell division. Caldesmon (CaD) is an actin-binding protein encoded by the CALD1 gene as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight CaD, expressed in smooth muscle, and low-molecular weight CaD (l-CaD), expressed in nonsmooth muscle cells. According to our comprehensive review of the literature, CaD, particularly l-CaD, plays a key role in the development, metastasis, and resistance to chemoradiotherapy in colorectal, breast, and urinary bladder cancers and gliomas, among other malignancies. CaD is involved in many aspects of the carcinogenic hallmarks, including epithelial mesenchymal transition via transforming growth factor-beta signaling, angiogenesis, resistance to hormonal therapy, and immune evasion. Recent data show that CaD is expressed in tumor cells as well as in stromal cells, such as cancer-associated fibroblasts, where it modulates the tumor microenvironment to favor the tumor. Interestingly, CaD undergoes selective tumor-specific splicing, and the resulting isoforms are generally not expressed in normal tissues, making these transcripts ideal targets for drug design. In this review, we will analyze these features of CaD with a focus on CRC and show how the currently available data qualify CaD as a potential candidate for targeted therapy in addition to its role in the diagnosis and prognosis of cancer.
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Affiliation(s)
- Alya R Alnuaimi
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
- College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Vidhya A Nair
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Lara J Bou Malhab
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Eman Abu-Gharbieh
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
- Department of Clinical Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Anu Vinod Ranade
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
- Department of Basic Medical Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Gianfranco Pintus
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
- Department of Medical Laboratory Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
- Department of Biomedical Sciences, University of Sassari, Sassari 07100, Italy
| | - Mohamad Hamad
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
- Department of Medical Laboratory Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Hauke Busch
- University Cancer Center Schleswig-Holstein and Luebeck Institute for Experimental Dermatology, University of Luebeck, Luebeck 23560, Germany
| | - Jutta Kirfel
- Institute of Pathology, University Hospital Schleswig-Holstein, Luebeck 23560, Germany
| | - Rifat Hamoudi
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
- Department of Clinical Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
- Division of Surgery and Interventional Science, University College London, London WC1E 6BT, United Kingdom
| | - Wael M Abdel-Rahman
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
- Department of Medical Laboratory Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
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Wu YL, Lang L, Ma Q, Wu F, Zhang Y, Chen W, Yan XC, Duan GJ. Perivascular Epithelioid Cell Tumor of Urinary Bladder. Am J Clin Pathol 2021; 156:56-71. [PMID: 33336255 DOI: 10.1093/ajcp/aqaa204] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVES To review the clinicopathologic features of perivascular epithelioid cell tumor (PEComa) of the urinary bladder. METHODS Seven cases of bladder PEComa were studied by light microscopy, immunohistochemistry, and fluorescence in situ hybridization (FISH). RESULTS In our 7 cases, 5 patients were female and 2 were male, with ages between 26 and 78 years. Patients presented with hematuria and recurrent abdominal discomfort as the main clinical symptoms. Microscopically, the epithelioid and spindle-shaped tumor cells with clear to granular eosinophilic cytoplasm were arranged in fascicular, acinar, or nested patterns. The tumor cells were positive for HMB45, melan-A, and SMA, but no TFE3 gene rearrangement was detected in any of the 7 samples by FISH. The analysis of all 35 cases from the literature and ours showed a patient age range from 16 to 78 years (mean age, 39 years), a male-to-female ratio of 1:1.3, maximal tumor diameters from 0.6 to 18.8 cm (mean, 4.5 cm). With a mean follow-up of 27 months, the recurrence, metastasis, and mortality rates were 10.7%, 10.7%, and 7.1%, respectively. CONCLUSIONS Bladder PEComa is extremely rare, remains a diagnostic challenge, and needs more attention. Strengthening the understanding of this tumor will improve diagnostic accuracy.
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Affiliation(s)
- You-li Wu
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Lang Lang
- Institute of Urology of PLA and Department of Urology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Qiang Ma
- Department of Pathology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Feng Wu
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yu Zhang
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Wei Chen
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiao-chu Yan
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Guang-jie Duan
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
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7
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Tee JL, Chambers J, Strutton G. Bladder perivascular epithelioid cell tumour and tuberous sclerosis complex: a rare association. BMJ Case Rep 2021; 14:14/5/e241635. [PMID: 34039545 DOI: 10.1136/bcr-2021-241635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Bladder perivascular epithelioid cell tumours (PEComas) associated with tuberous sclerosis complex (TSC) are rare, with only one other case report in the literature to date. We present our case of a bladder PEComa in a young adult female with TSC arising de novo. Histopathology showed features in keeping with an angiomyolipoma and confirmatory immunohistochemical stains were positive for both melanocytic and smooth muscle markers. She was well at the 6-month follow-up post-surgical resection. Given the rarity of such lesions in the bladder, we discuss the diagnostic and prognostic challenges, clinical implications and a brief review of the literature to date.
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Affiliation(s)
- Jo Lin Tee
- Anatomical Pathology, Pathology Queensland, Queensland Health, Brisbane, Queensland, Australia
| | | | - Geoffrey Strutton
- Anatomical Pathology, Pathology Queensland, Queensland Health, Brisbane, Queensland, Australia
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8
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Histopathologic Characterization of Bladder Perivascular Epithelioid Cell Neoplasms (PEComa): A Series of 11 Cases With a Subset Having TFE3 Rearrangements. Am J Surg Pathol 2021; 45:169-177. [PMID: 33002920 DOI: 10.1097/pas.0000000000001592] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Perivascular epithelioid cell neoplasms (PEComas) of the bladder are extremely rare, with ~30 case reports. A subset of PEComas contain TFE3 gene rearrangement, however, the distinct histomorphologic features of these translocation tumors has not been fully explored in bladder PEComas. In our series, 11 cases of bladder PEComas were collected, including 1 internal and 10 consults, with 1 case previously reported. There was a female predominance (9 female, 2 male) with a mean age of 44.2 years (24 to 61 y). In only 1 of the 10 consult cases was PEComa considered in the differential diagnosis. In 10 of 11 cases, prominent epithelioid features were noted, with the final case having focal epithelioid morphology. Mitotic rate was increased in 2 of 11 cases, and 2 of 11 cases had cytological atypia. Two cases were malignant, with invasion into perivesicle tissue in 1 case, and metastases to lungs and brain followed by death in the other case. Immunohistochemically, there was strong, and diffuse staining for cathepsin K in 10/11 cases with the 1 negative case restained on a previously stained slide. HMB-45 was diffusely positive in 8/11 cases, while melan-A was present in only 1/10 cases. Muscle markers were variably expressed with positivity for both smooth muscle actin in 6/10 cases and desmin in 3/10 cases. Keratin AE1/3 was uniformly negative (0/11). In 5/8 cases where TFE3 was rearranged by fluorescence in situ hybridization, the morphology had a predominantly epithelioid, nested architecture. Overall, bladder PEComas are particularly difficult to diagnose given their rarity, are predominantly epithelioid and do not always express melanocytic markers. Diagnosis in the bladder requires a combination of morphologic characterization, exclusion of other diagnostic possibilities, positive Cathepsin K staining, variable melanocytic marker expression, with some cases showing a TFE3 gene rearrangement.
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