Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma

Abstract

Introduction: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. Methods: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. Results and conclusion: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers’ expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

Tislelizumab with gemcitabine and cisplatin as a neoadjuvant regimen for muscle-invasive bladder cancer: case series

“…Although our regimen increased and decreased tumour CK5 and GATA3, respectively, suggesting a luminal-to-basal transition, studies with larger sample size are needed. In addition, Ki67 expression appeared to be associated with UBC aggressiveness evidenced by higher grade, muscle invasion, and increased postoperative circulating tumour cells 35 , 36 . All three patients in our study had relatively high levels of Ki67 and all responded well to the treatment, suggesting the levels of Ki67 might be an indicator of responsiveness.…”

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“…On histopathology, there are four defined layers for the urinary bladder wall: the urothelium (lines the bladder lumen); submucosa (the vascular lamina propria ); the muscularis propria (important prognostic landmark if the tumour invades) ; and the outermost serosal 27 , 28 .…”

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“…Since the discovery of p16 more than 20 years ago, numerous scientific studies on its regulation and function have proven its complex nature. The role of p16 extends beyond cell “aging” and tumor pathology[ 25 , 26 ].…”