1.Expression of pRb, p53, p16 and Cyclin D1 and Their Clinical Implications in Urothelial Carcinoma.
Kyungji LEE ; Eun Sun JUNG ; Young Jin CHOI ; Kyo Young LEE ; Ahwon LEE
Journal of Korean Medical Science 2010;25(10):1449-1455
The aim of this study was to assess immunohistochemical expression of p53, pRb, p16, and cyclin D1, alone or in combination, as prognostic indicators and to investigate their correlation with clinocopathologic features of urothelial carcinoma. Immunohistochemical staining for p53, pRb, p16, and cyclin D1 was performed on a tissue microarray from 103 patients with urothelial carcinoma who underwent radical cystectomy. Of the patient samples analyzed, 36 (35%), 61 (59%), 47 (46%) and 30 (29%) had altered expression of p53, pRb, p16, and cyclin D1, respectively. Abnormal expression of p53 and pRb correlated with depth of invasion (P=0.040 and P=0.044, respectively). Cyclin D1 expression was associated with tumor stage and recurrence (P=0.017 and P=0.036, respectively). Altered pRb was significantly correlated with overall survival (P=0.040). According to the expression pattern of pRb and p53, p53/pRb (altered/normal) had worse survival than p53/pRb (normal/altered) (P=0.022). Alteration of all markers had worse survival than all normal (P=0.029). As determined by multivariate analysis, tumor stage, lymph node metastasis and the combined expression of p53 and pRb are independent prognostic factors. In conclusion, immunohistochemical evaluation of cell cycle regulators, especially the p53/pRb combination, might be useful in planning appropriate treatment strategies.
Adult
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Aged
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Aged, 80 and over
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Carcinoma, Transitional Cell/*metabolism/mortality/pathology
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Cyclin D1/*metabolism
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Cyclin-Dependent Kinase Inhibitor p16/*metabolism
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Female
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Humans
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Immunohistochemistry
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Lymphatic Metastasis
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Male
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Middle Aged
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Multivariate Analysis
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Neoplasm Staging
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Prognosis
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Recurrence
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Retinoblastoma Protein/*metabolism
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Survival Rate
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Tumor Suppressor Protein p53/*metabolism
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Urinary Bladder Neoplasms/*metabolism/mortality/pathology
2.Fibroblast Growth Factor Receptor 1 Overexpression Is Associated with Poor Survival in Patients with Resected Muscle Invasive Urothelial Carcinoma.
Seungtaek LIM ; Myoung Ju KOH ; Hyeon Joo JEONG ; Nam Hoon CHO ; Young Deuk CHOI ; Do Yeun CHO ; Hoi Young LEE ; Sun Young RHA
Yonsei Medical Journal 2016;57(4):831-839
PURPOSE: To examine the usefulness of various receptor tyrosine kinase expressions as prognostic markers and therapeutic targets in muscle invasive urothelial cancer (UC) patients. MATERIALS AND METHODS: We retrospectively analyzed the data of 98 patients with muscle invasive UC who underwent radical cystectomy between 2005 and 2010 in Yonsei Cancer Center. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemical staining was done for human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 3 (FGFR3). RESULTS: There were 41 (41.8%), 44 (44.9%), and 14 (14.2%) patients who have over-expressed HER2, FGFR1, and FGFR3, respectively. In univariate analysis, significantly shorter median time to recurrence (TTR) (12.9 months vs. 49.0 months; p=0.008) and overall survival (OS) (22.3 months vs. 52.7 months; p=0.006) was found in patients with FGFR1 overexpression. By contrast, there was no difference in TTR or OS according to the HER2 and FGFR3 expression status. FGFR1 remained as a significant prognostic factor for OS with hazard ratio of 2.23 (95% confidence interval: 1.27-3.90, p=0.006) in multivariate analysis. CONCLUSION: Our result showed that FGFR1 expression, but not FGFR3, is an adverse prognostic factor in muscle invasive UC patients after radical cystectomy. FGFR1 might be feasible for prognosis prediction and a potential therapeutic target after thorough validation in muscle invasive UC.
Adult
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Aged
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Aged, 80 and over
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Carcinoma/*metabolism/*mortality/surgery
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Cystectomy
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Female
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Humans
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Male
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Middle Aged
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Multivariate Analysis
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Muscles/pathology
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Neoplasm Invasiveness
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Prognosis
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Proportional Hazards Models
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Receptor, ErbB-2/metabolism
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Receptor, Fibroblast Growth Factor, Type 1/*metabolism
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Receptor, Fibroblast Growth Factor, Type 3/metabolism
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Retrospective Studies
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Survival Rate
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Urinary Bladder Neoplasms/*metabolism/*mortality/surgery
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Urothelium/pathology
3.Novel Combination Markers for Predicting Survival in Patients with Muscle Invasive Bladder Cancer: USP18 and DGCR2.
Ye Hwan KIM ; Won Tae KIM ; Pildu JEONG ; Yun Sok HA ; Ho Won KANG ; Seok Joong YUN ; Sung Kwon MOON ; Yung Hyun CHOI ; Isaac Yi KIM ; Wun Jae KIM
Journal of Korean Medical Science 2014;29(3):351-356
We performed gene expression profiling in bladder cancer patients to identify cancer-specific survival-related genes in muscle invasive bladder cancer (MIBC) patients. Sixty-two patients with MIBC were selected as the original cohort and another 118 MIBC patients were chosen as a validation cohort. The expression of USP18, DGCR2, and ZNF699 genes were measured and we analyzed the association between gene signatures and survival. USP18 and DGCR2, were significantly correlated to cancer-specific death (P=0.020, P=0.007, respectively). Cancer-specific survival in the low USP18 or DGCR2 expression group was significantly longer than the high expression group (P=0.018, P=0.006, respectively). In multivariate Cox regression analysis, a combination of USP18 and DGCR2 mRNA expression levels were significant risk factors for cancer-specific death (HR, 2.106; CI, 1.043-4.254, P=0.038). Overall survival and cancer-specific survival rates in the low-combination group were significantly longer than those in the high-expression group (P=0.001, both). In conclusion, decreased expressions of USP18 and DGCR2 were significantly associated with longer cancer-specific survival, and also the combination of two genes was correlated to a longer survival for MIBC patients. Thus, the combination of USP18 and DGCR2 expression was shown to be a reliable prognostic marker for cancer-specific survival in MIBC.
Adult
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Aged
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Aged, 80 and over
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Biological Markers/metabolism
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Carrier Proteins/genetics/metabolism
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Endopeptidases/genetics/*metabolism
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Female
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Gene Expression Profiling
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Humans
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Kaplan-Meier Estimate
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Male
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Middle Aged
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Muscle Neoplasms/*secondary
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Neoplasm Invasiveness
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Neoplasm Staging
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Platelet Glycoprotein GPIb-IX Complex/genetics/*metabolism
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Predictive Value of Tests
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ROC Curve
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Regression Analysis
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Risk Factors
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Urinary Bladder Neoplasms/*diagnosis/metabolism/*mortality/pathology