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Taghipour Zahir S, Razavi SH, SafiDahaj F, Rahmani K, Sadeghinejad‐Alamabadi S. Prognosis and survival study in patients with gastric adenocarcinoma and its relationship with pRb expression alteration: A retrospective IHC-based study. Health Sci Rep 2023; 6:e1445. [PMID: 37519424 PMCID: PMC10372302 DOI: 10.1002/hsr2.1445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 03/25/2023] [Accepted: 07/14/2023] [Indexed: 08/01/2023] Open
Abstract
Background and Objective Among cancers, gastric cancer has the fifth highest incidence worldwide and is the third most common mortality factor, which may have been due to inadequate knowledge of its molecular pathogenesis. The retinoblastoma gene (RB1), a tumor suppressor gene, may have a role in gastric cancer. This research aims to assess Rb expression as a prognostic marker to obtain more insight regarding gastric cancer. Methods This retrospective analytical study was done on 61 patients (45 males and 16 females) with gastric adenocarcinoma admitted from 2010 to 2012 in Shahid Sadoughi and Mortaz hospitals, Yazd, Iran. Demographic data, including age, gender, clinical signs and symptoms, and pathology reports, were retrieved from patients' hospital folders. Then, the altered Retinoblastoma gene expression was evaluated by immunohistochemistry studies. Acquired data were analyzed by SPSS software v.16. p < 0.05 was statistically considered meaningful. Results In this study, the ratio of men to women was higher (2.81:1), and the mean age of patients was 62.44 years. About 90.2% of patients died during the study. There was no meaningful relationship between the presence of pRb, the intensity of staining, the percentage of staining with patients' age, gender, tumor grading, and survival rate (p > 0.05). There was only a meaningful relationship between the grade of tumors and survival rate (p = 0.039). Conclusion Altered pRB expression is not common in gastric cancer and does not impact the survival and grading of tumors. Poorly differentiated tumors had an ominous outcome with the lowest survival time.
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Affiliation(s)
| | - Seyyed Hossein Razavi
- Clinical and Surgical PathologyShahid Sadoughi University of Medical SciencesYazdIran
| | - Farzan SafiDahaj
- Clinical and Surgical PathologyShahid Sadoughi University of Medical SciencesYazdIran
| | - Koorosh Rahmani
- Clinical and Surgical PathologyShahid Sadoughi University of Medical SciencesYazdIran
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Expression of pRb, Ki67 and HER 2/neu in gastric carcinomas: Relation to different histopathological grades and stages. Ann Diagn Pathol 2017; 30:1-7. [PMID: 28965621 DOI: 10.1016/j.anndiagpath.2017.05.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Revised: 04/11/2017] [Accepted: 05/10/2017] [Indexed: 12/18/2022]
Abstract
Gastric carcinoma is one of the aggressive malignancies with poor prognosis. The expression of pRb, Ki67, Her-2 in relation to tumor grade and stage in gastric carcinoma still needs more exploration. This study was performed aiming to study the immunohistochemical expression of altered retinoblastoma encoding protein (pRb), Ki67 and Her-2 in gastric carcinoma and to investigate their clinical and pathological significance. We studied tumor tissue specimens from 48 patients with gastric carcinoma. Paraffin sections were submitted for immunohistochemistry using pRb, Ki67 and Her-2. Statistical analysis was performed for clinical and pathological data of all studied cases. Altered pRb was expressed in 79% of the studied tumors, inversely correlated with tumor invasion and stage with no significant relation with tumor grade, age, and gender and tumor size. Ki67 LI was significantly associated with tumor grade and stage but not related to sex, age, tumor size, site, depth of invasion and lymph node metastasis. Her2 was expressed in 75% of studies tumors with significant association with tumor grade, the depth of invasion, lymph node metastasis and higher tumor stage. However, there was no significant association between Her-2 expression and gender, tumor site and size. In conclusion, altered pRb is frequently expressed in gastric carcinoma, inversely correlates with tumor invasion and tumor stage suggesting an early event in gastric carcinogenesis. Ki67 expression in gastric carcinoma is directly correlated with the tumor grade and depth of invasion. Her2 expression is significantly correlated with tumor grade, depth of invasion and stage.
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Chou NH, Chen HC, Chou NS, Hsu PI, Tseng HH. Expression of altered retinoblastoma protein inversely correlates with tumor invasion in gastric carcinoma. World J Gastroenterol 2006; 12:7188-7191. [PMID: 17131485 PMCID: PMC4087784 DOI: 10.3748/wjg.v12.i44.7188] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2006] [Revised: 09/28/2006] [Accepted: 11/18/2006] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the clinical and pathological significance of altered retinoblastoma (Rb) encoding protein (pRb) in gastric carcinoma. METHODS Expression of altered pRb was analyzed in 91 patients with gastric adenocarcinoma by immunohistochemistry. RESULTS Sixty-five percent (59/91) of the tumors were positively stained and the staining in tumor nuclei of gastric carcinoma ranged 0%-90%. Moreover, strong expression of altered pRb was found in 35% (6/17), 24% (5/21), 17% (8/46) and 0% (0/7) of T1, T2, T3 and T4 gastric carcinomas, respectively. Altered pRb expression was inversely correlated with the depth of tumor invasion (P = 0.047). Degree of immunoreactivity had no significant correlation with tumor grade, node metastasis and distant metastasis. In terms of prognostic significance, univariate analysis showed that poor differentiation [41 (66.1%) vs 34 (42.5%) P = 0.051], advanced tumor stage (P < 0.001) and weakly altered pRb expression [17 (80.5%) vs 58 (49.6%) P=0.044] were associated with worse prognosis in these patients. However, multivariate analysis revealed that advanced tumor stage was the only independent poor prognostic factor (P < 0.001). CONCLUSION the mutation of Rb gene is frequent in gastric carcinoma. The expression of altered pRb inversely correlates with tumor invasion and is not an independent prognostic marker in gastric adenocarcinoma.
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Affiliation(s)
- Nan-Hua Chou
- Department of Surgery, Veterans General Hospital-Kaohsiung 386, Ta-Chung 1st Rd, Kaohsiung, 813, Taiwan, China.
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Takada H, Imoto I, Tsuda H, Sonoda I, Ichikura T, Mochizuki H, Okanoue T, Inazawa J. Screening of DNA copy-number aberrations in gastric cancer cell lines by array-based comparative genomic hybridization. Cancer Sci 2005; 96:100-10. [PMID: 15723654 PMCID: PMC11160020 DOI: 10.1111/j.1349-7006.2005.00016.x] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
We performed genome-wide screening for deoxyribonucleic acid copy-number aberrations in 31 gastric cancer (GC) cell lines by using custom-made comparative genomic hybridization (CGH)-array. Copy-number gains were frequently detected at 1q, 3q, 5p, 7p, 7q, 8q, 11q, 17q, 20p, 20q, Xp and Xq, and losses at 3p, 4p, 4q, 8p, 9p, 18p and 18q. With respect to histological subtypes, copy-number gains at 1p, 16p, 20p, 20q and 22q, and losses at 8p, 10p, 10q and 18q were significantly frequent in cell lines derived from tumors of the well-differentiated type, whereas copy-number gains at 1q, 7p, 7q, Xp and Xq were frequent in the undifferentiated type. Homozygous deletions were seen at five loci, whereas high-level amplifications were detected in 15 of the 31 GC cell lines; these had occurred at 24 loci, including the segment containing CDK6 (7q21.2). Amplification of that gene had never been reported in GC before. Immunohistochemical studies showed increased levels of CDK6 protein in 54 of the 292 primary GC samples we examined (18.5%). Cytoplasmic localization of CDK6, as well as CDK6 over-expression, was more frequent in well-differentiated GC than in undifferentiated tumors. Nuclear expression of CDK6 was more frequent in early stage GC than in advanced tumors, suggesting that nuclear localization of CDK6 is likely to be a prognostic factor for GC. Taken together, our data indicate that CDK6 might be involved in the pathogenesis of GC and, more generally, that CGH-arrays have a powerful potential for identifying novel cancer-related genetic changes in a variety of tumors.
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Affiliation(s)
- Hisashi Takada
- Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510, Japan
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Chetty R, Subramoney T, Singh JP. Retinoblastoma and p53 protein expression in sporadic colorectal cancers. Eur J Surg Oncol 1998; 24:436-9. [PMID: 9800976 DOI: 10.1016/s0748-7983(98)92434-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023] Open
Abstract
AIMS To ascertain if a relationship between retinoblastoma (pRb) and p53 proteins exists in sporadic colorectal carcinomas. METHODS Fifty consecutive colectomy specimens for colorectal cancer in patients over the age of 50 and with no family history of cancers in the bowel were examined for immunoexpression of pRb and p53 proteins. These findings were then related to clinicopathological findings. Commercially available monoclonal antibodies to pRb and p53 were used on formalin-fixed, paraffin-embedded tissue. RESULTS The most intense pRb immunoexpression was detected in well-differentiated, low-stage cancers. On the other hand, p53 expression was most intense in poorly differentiated, advanced-stage carcinomas. No statistically significant associations were noted with immunoexpression and age, gender or site of lesion. CONCLUSIONS This study indicates that there is an inverse relationship between pRb and p53 protein expression in a proportion of sporadic colorectal cancers. Twelve tumours which showed low levels of pRb showed high levels of p53 protein. Similarly, seven tumours with high pRb levels displayed low p53 expression. In terms of immunohistochemical profile, p53-high/pRb-low tumours tended to be poorly differentiated and have advanced stage cancer.
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Affiliation(s)
- R Chetty
- Department of Pathology, University of Natal School of Medicine, Durban, South Africa.
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Abstract
The aim of this study was to explore the expression of retinoblastoma protein and EBV status in a cohort of cases of Hodgkin's disease from South Africa. Seventy one cases of Hodgkin's disease were accessed over a 6-year period and were classified according to the Rye Classification. Relevant sections were stained with commercially available antibodies to retinoblastoma protein (pRb) and EBV-LMP-1. In addition, in situ hybridization for EBERs was also performed. The results of this study show that 43 of 71 cases expressed EBV by both immunohistochemistry and in situ hybridization. These included 18 mixed cellularity, 19 nodular sclerosis and six lymphocyte depleted subtypes. pRb expression was seen in lymphocytes, mononuclear Hodgkin's and Reed-Sternberg cells in 67 of the cases. From this study it appears that pRb expression is seen in the majority of cases of Hodgkin's disease: 67/71 (94.4 per cent). Thirty-nine of 43 cases (90.7 per cent) of EBV positive cases were also positive for pRb. The results of this study indicate that pRb immunoexpression is detected in the vast majority of cases of Hodgkin's disease, and that this expression is independent of the EBV status of the case.
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Affiliation(s)
- R Chetty
- Department of Pathology, University of Natal School of Medicine, Durban, South Africa
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Chetty R, Chetty S. Cyclin D1 and retinoblastoma protein expression in oesophageal squamous cell carcinoma. Mol Pathol 1997; 50:257-60. [PMID: 9497916 PMCID: PMC379642 DOI: 10.1136/mp.50.5.257] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIMS To assess the immunoexpression of cyclin D1 and retinoblastoma in a cohort of oesophageal squamous cell carcinoma cases from South Africa to see whether there is a relation between these two proteins. In addition, protein expression was correlated with clinicopathological features. METHODS Fifty biopsies and 30 oesophagectomy specimens were immunostained with commercially available antibodies to cyclin D1 and retinoblastoma proteins, following microwave antigen retrieval. RESULTS Twenty three of the 80 cases (29%) showed cyclin D1 protein expression. However, only five cases had > 50% of the tumour cells displaying immunopositivity. Three of the four cases with lymph node spread were cyclin D1 positive in the primary tumour and the metastasis. Fifty three cases were immunoreactive with the antiretinoblastoma antibody; 29 of these cases showing > 50% of cells with immunolabelling. Of the 23 cyclin D1 positive cases, 18 were also retinoblastoma positive. No correlation was observed between cyclin D1 and retinoblastoma protein expression and age, sex, race, or histological grade. CONCLUSIONS Cyclin D1 is expressed in a minority of cases of oesophageal squamous carcinomas from South Africa. However, three of four cases with lymph node spread were cyclin D1 positive, thus indicating that cyclin D1 positive tumours may have a greater propensity for spread. In addition, 18 of 23 cyclin D1 positive cases also expressed retinoblastoma protein. These findings suggest a possible relation between cyclin D1 and retinoblastoma proteins in a proportion of cases of oesophageal squamous.
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Affiliation(s)
- R Chetty
- Department of Anatomical Pathology, University of Natal School of Medicine, Congella, Durban, South Africa
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Lai S, Benedict WF, Silver SA, El-Naggar AK. Loss of retinoblastoma gene function and heterozygosity at the RB locus in renal cortical neoplasms. Hum Pathol 1997; 28:693-7. [PMID: 9191003 DOI: 10.1016/s0046-8177(97)90178-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Alteration of the retinoblastoma (RB) gene, located on chromosome 13q14, has been implicated in the pathogenesis and biological behavior of several human cancers. We investigated the RB gene status by Western blotting and immunohistochemical analysis, as well as loss of heterozygosity (LOH) at the RB locus in 21 primary human renal neoplasms (including 3 oncocytomas). In only 1 of 21 tumors was there a discrepancy between Western blot and immunochemical staining. Overall, LOH was noted in 6 of 12 informative cases. However, only one of the tumors with LOH at the RB locus had loss of RB protein expression by both Western blot and immunohistochemical analysis. Loss of RB function was found in 4 of 18 carcinomas and in none of 3 oncocytomas as determined by absent RB nuclear staining in tumor cells. LOH at chromosome 13q14 was more noted in high-grade, DNA aneuploid, high-stage tumors and in patients with poor outcome. These results imply that (1) there is likely another tumor-suppressor gene on chromosome 13 involved in renal carcinogenesis, (2) LOH at chromosome 13q loci may be associated with aggressive behavior, and (3) the loss of RB function may have a role in a subset of renal carcinomas.
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Affiliation(s)
- S Lai
- Department of Pathology, the University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA
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Ogawa M, Maeda K, Onoda N, Chung YS, Sowa M. Loss of p21WAF1/CIP1 expression correlates with disease progression in gastric carcinoma. Br J Cancer 1997; 75:1617-20. [PMID: 9184177 PMCID: PMC2223544 DOI: 10.1038/bjc.1997.276] [Citation(s) in RCA: 48] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Previous studies have shown that tumour-suppressor genes play an important role in the progression of solid tumours. Recently, the p21WAF1/CIP1 tumour-suppressor protein has been reported to work as a critical downstream effector of p53 and a potent inhibitor of cyclin-dependent kinases. Thus, the p21WAF1/CIP1 gene is thought to play a central role in tumour suppression. In this study we investigated p21 protein expression in gastric carcinomas. A total of 172 primary gastric carcinoma specimens were immunohistochemically stained for p21 protein expression. Correlations between p21 expression and clinicopathological features were examined. Loss of p21 expression was observed in 104 of 172 tumour tissues (60.4%), and the frequency of p21 loss increased as the stage progressed. Expression of p21 in the primary tumour was frequently lost in patients with either lymph node, liver or peritoneal metastases as compared with patients without metastases. In patients with p21-negative tumours, the risk of recurrence following curative surgery was significantly higher, and the prognosis was significantly poorer than in patients with p21-positive tumours. Loss of p21 expression in primary gastric carcinoma correlates with disease progression. The status of p21 gene expression may have prognostic value in this disease.
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Affiliation(s)
- M Ogawa
- First Department of Surgery, Osaka City University Medical School, Abeno-ku, Japan
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Ito Y, Kobayashi T, Takeda T, Komoike Y, Wakasugi E, Tamaki Y, Umeshita K, Monden T, Monden M. Immunohistochemical study of Cell Cycle Modulators in G(1)-S Transition in Clinical Breast Cancer Tissue. Breast Cancer 1996; 3:93-104. [PMID: 11091560 DOI: 10.1007/bf02966969] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
In the present study, we investigated immunolocalization of the modulators of G(1)-S transition by using monoclonal or polyclonal antibodies for each of the modulators in 65 cases of clinical breast cancer. Two prominent cyclin dependent kinase(cdk)-cyclin complexes, cdk4-cyclin D and cdk2-cyclin E, were proved to have different modes of mutual expression. cdk4-positive lesions were found to equal cyclin D-expressing lesions in 55 cases, while the former were more extensive than the latter in 9 cases. On the other hand, cyclin E expression was detected in all the cases examined and was more dominant than that of cdk2/cdc2 in as many as 40 cases whereas the reverse was seen in only 1 case. Interestingly, cdk4(P<0.01)and cyclin E(P<0.05)expressions showed an inverse relationship with the tumor size and the cancer stage. A similar tendency was also detected for two other positive modulators of G(1)-S transition, indicating that cell cycle progression must be regulated by the cancer itself once it has grown to a certain extent. p21, which has been regarded as a universal inhibitor of the cell cycle, was expressed in 43.1% of the cases examined and its immunoreactivity showed an inverse relationship with lymph node metastasis(P<0.05). It also tended to be absent more frequently in T3 or larger cancers and stage III cases. Moreover, two patients who died as a result of cancer and three patients with recurrence were all p21 negative, suggesting that p21 is prognosticably the most significant of all these modulators.
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Affiliation(s)
- Y Ito
- Departments of Surgery II, Osaka University Medical School, 2-2 Yamadaoka, Suita 565, Japan
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