The prognostic significance of p63 cytoplasmic expression in colorectal cancer. An immunohistochemical study

Abstract

Objectives: To evaluate p63 expression pattern in Saudi colorectal cancer (CRC) patients and correlate that with clinicopathological parameters and its role in carcinogenesis and prognosis.

Methods: Archival tumor samples were analyzed by immunohistochemistry for p63 expression in 324 consecutive Saudi patients diagnosed with CRC between January 2006 and December 2017 at the Pathology Department of a tertiary care Hospital, Madinah, Saudi Arabia.

Results: P63 over-expression was absent in normal mucosa, while 12.5% cases of adenoma showed its over-expression. In CRC, p63 expression was high in 24.1% of cases. There were no significant correlations between p63 expression and gender, tumor location, tumor size and tumor histologic differentiation. However, high p63 expression revealed a significant correlation with age (p=0.035), tumor type (p=0.004), American Joint Committee on Cancer stage (p=0.046), lymph node metastasis (p=0.006), lymphovascular invasion (p=0.006), distant metastasis (p=0.049), high Ki67 expression (p=0.000) and K-ras expression (p=0.002). The Kaplan-Meier analysis revealed a shorter period of survival with p63 over-expression (p less than 0.001). The Cox-regression model analysis showed that p63 over-expression was an independent prognostic marker in CRC (p=0.000).

Conclusion: P63 expression was increased from normal to adenoma to carcinoma sequence. Moreover, p63 cytoplasmic expression seems to be related to high Ki67 indexing, K-ras expression, advanced tumor stage and poor clinical outcome of CRC. These findings suggest a significant role of cytoplasmic p63 expression in tumor progression and prognosis.

Figure 1

Photomicrograph of different patterns of p63 expression by immunohistochemistry in A) normal colonic mucosa showing a negative expression of p63, B) colorectal adenoma showing cytoplasmic expression of p63 in the tumor cells, C) colorectal carcinoma showing intense cytoplasmic expression of p63 in tumor cells. Red arrows indicate cytoplasmic expression of p63, and D) a control sample from normal prostate gland showing intense selective nuclear expression of p63 in basal cell layer. Black arrow indicates nuclear expression of p63.

Figure 2

Kaplan-meier survival curves showing significant overall lower survival functions for high p63 expression in colorectal cancer cases.