Expression of p16 in Urothelial Carcinoma of Urinary Bladder and its Association with Histologic Grade and Invasion: A Cross-sectional Study from Kerala, India

Abstract

Introduction: Bladder cancer is the seventh most common cancer worldwide and is the most prevalent malignant neoplasm of the urinary tract. More than 90% of bladder cancer cases are urothelial (transitional cell) carcinoma. Histologic grading is one of the most important prognostic factors in bladder cancer. Based on infiltration, it is classified as invasive or non invasive, and further categorised as high-grade or low-grade carcinoma. The management and prognosis of patients is based on the accurate grading of these tumours. Loss of p16 has been found to be associated with high-grade tumours and invasion in urothelial carcinoma. Understanding the expression of p16 can aid in determining the grade of the tumour and predicting its invasive nature. Aim: To study the expression of p16 and its association with the grade and invasiveness of urothelial carcinoma of the urinary bladder. Materials and Methods: This study was a cross-sectional study, done over a period of one year and six months, from December 2019 to May 2021, in the Department of Pathology at Pushpagiri Institute of Medical Sciences in Thiruvalla, a tertiary care centre in South Kerala, India. A total of 37 cases of urothelial carcinoma were selected for histomorphological and Immunohistochemical (IHC) evaluation, and the results were analysed using Statistical Package for the Social Sciences (SPSS) version 16.0. The IHC panel used was mouse monoclonal p16 antibody. The frequency of p16 expression, along with its association with age, gender, grade, and invasion in urothelial carcinoma, was studied. Results: There 14 cases of invasive urothelial carcinoma, among which 11 cases (78.57%) showed loss of p16 with a negative staining pattern, one showed normal staining, and two cases showed high expression. Most of the non invasive tumours, comprising 21 cases (91.30%) showed normal p16 expression, while two cases showed high p16. In the present study, there were 18 cases of high-grade urothelial carcinoma, 11 cases showed loss of p16 with a negative staining pattern, four cases showed normal staining, and three cases showed high p16 expression. There were 19 cases of low-grade urothelial carcinoma; 18 of which showed low/normal p16 expression, and one case showed overexpression of p16. Conclusion: p16 was found to be negative or lost in high-grade and invasive urothelial carcinomas. Analysing the expression of p16 can aid in determining the grade and invasive nature of the lesion, especially when biopsy samples are limited, in the absence of deep biopsy, or when muscle tissue is not sampled, and when tissue architecture is altered by cautery artifacts.

Keywords

• immunohistochemistry
• muscle invasion
• pathogenesis
• treatment