Abstract

Backgroundp16 is the protein product of most commonly involved gene in bladder carcinogenesis. Therefore, we performed an immunohistochemical study to evaluate association of p16 overexpression with prognostic parameters in bladder cancer.Methodsp16 immunohistochemistry was performed on 121 cases of bladder cancer and association with tumor grade, lamina propria invasion, muscularis propria invasion and survival status was noted.ResultsLow expression of p16 was noted in 86% (104 cases), whereas 14% (17 cases) revealed high p16 expression. We found significant association of p16 expression with tumor grade (p = 0.000), muscularis propria invasion (p = 0.001), lamina propria invasion (p = 0.001) and survival status (p = 0.020). Univariate binary logistics showed that low grade tumors were less likely to express high p16 expression as compared to high grade tumors. Similarly, patients with lamina propria and muscularis propria invasion were more likely to exhibit high p16 expression. Significant association of high p16 expression was noted with worse long term survival (p = 0.020), while univariate logistic regression showed that patients with low p16 expression were at low risk (HR = 0.194) to die of disease as compared to patients with high p16 expression.Conclusionp16 is an important biomarker in bladder cancer as it can be used for prognostic stratification of patients with bladder cancer. Moreover, we suggest that molecular studies should be performed in our population in order to correlate abnormal p16 expression with underlying gene mutations.

Highlights

  • Urothelial carcinoma is the most common morphologic type of bladder cancer

  • In the current study, we found that high expression of p16 to be associated with higher grade and poor prognostic factors including muscularis propria invasion and poor long term survival

  • In most of the studies analyzed, IHC markers were used to evaluate p16 expression and marked heterogeneity exists in the definition of abnormal IHC expression of p16. p16 is a tumor suppressor gene, which is most commonly involved in bladder carcinogenesis

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Summary

Introduction

Urothelial carcinoma is the most common morphologic type of bladder cancer. Chromosome 9p21 is the region which is most commonly altered in the onco-pathogenesis of bladder cancer. P16 is the most important gene which is either deleted or mutated in this process. P16 is a tumor suppressor gene; loss of its function results in abnormal cell proliferation leading to cancer development (Cairns et al, 1995; Williamson et al, 1995). Prognostic parameters of bladder cancer include histologic differentiation, grade, lamina propria invasion and deep muscle invasion. Hashmi et al Surgical and Experimental Pathology. High Expression (n = 17) Gender Male 77 (74) 11 (64.7) Female 27 (26) 6 (35.3) Age group

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