Expression of p16INK4a, Alone or Combined With p53, is Predictive of Better Prognosis in Colorectal Adenocarcinoma in Tunisian Patients

Introduction: Alterations in different signaling pathways are involved in initiation and progression of colorectal carcinoma, such as those related to p53, MLH1, p16INK4a, Kras, etc. Aim: This study was conducted with the aim to investigate the expression of p16INK4a and p53 in colorectal cancer (CRC) and evaluated their correlation with major clinicopathologic features and patients' survival. Materials and Methods: The expression of p16INK4a and p53 were analyzed by immunohistochemistry on 70 paraffin specimens of CRC. Results: Positive immunostaining for p16INK4a and p53 was observed in 27 (38.6%) and 53 (80%) cases, respectively. Significant correlation between loss of p16INK4a expression and tumor size was found (P = 0.008), whereas overexpression of p16INK4a correlated with favorable prognosis parameters, such as absence of lymph node metastasis (P = 0.029) and early stage of CRC (P = 0.027). Furthermore, p53 overexpression significantly correlated with distal tumor location (P = 0.022) and was related to a better overall survival in the group of patients with distal colon carcinomas (P = 0.002). Patients with p16INK4a-positive tumors had a significant longer overall survival time than patients with p16INK4a-negative carcinomas (P = 0.033). In addition, Cox regression model showed that overexpression of p16INK4a is an independent factor for prognosis with depth of invasion, p53 accumulation, and coincident abnormal expression of p16INK4a or p53. Conclusion: Our data suggest that the assessment of both p53 and p16INK4a expression might be helpful in predicting prognosis in patients with colorectal cancer.