# Immunohistochemical Expression of p16, p53, BCL2, and Cyclin D1 in Gastrointestinal Stromal Tumors: Correlation With Clinicopathological Parameters

## TL;DR

This study examines the expression of p16, p53, BCL2, and Cyclin D1 in gastrointestinal stromal tumors and their links to tumor behavior and patient outcomes.

## Contribution

The study identifies p16 and p53 as potential independent prognostic markers for recurrence and metastasis in GISTs.

## Key findings

- p16 and p53 expression were significantly associated with aggressive tumor behavior and poor survival outcomes.
- p16 was an independent predictor of local recurrence and distant metastasis in GISTs.
- BCL2 and Cyclin D1 showed mixed or uncertain prognostic value despite some associations with tumor aggressiveness.

## Abstract

Introduction

Gastrointestinal stromal tumors (GISTs) represent the predominant mesenchymal neoplasms within the gastrointestinal tract. Although some clinicopathological features can help estimate the risk of tumor progression, there is still a need for more reliable immunohistochemical markers to predict the tumor’s behavior. The current study aims to evaluate the immunohistochemical expression of p16, p53, BCL2, and Cyclin D1 in GISTs and to analyze their correlations with the clinicopathological characteristics and survival outcomes of the studied cases.

Methods

This retrospective cohort study included 65 cases of GISTs, retrieved from the archive of the Pathology Laboratory at the Gastroenterology Center, Mansoura University, between 2014 and 2018. Patients’ clinical and pathological data were revised. Three tissue microarray blocks were constructed. Immunohistochemical staining for p16, p53, BCL2, and Cyclin D1 was performed. Clinicopathological correlation and survival analysis were analyzed using appropriate statistical methods.

Results

In this study, p16, p53, BCL2, and Cyclin D1 expressions were observed in 15 cases (23.1%), 21 cases (32.3%), 52 cases (80%), and 57 cases (87.7%), respectively. Regarding p16 expression, it was significantly associated with tumor site, risk category, mitotic index, local recurrence, distant metastasis, lymph node involvement, and the expression of CD117, BCL2, p53, and Cyclin D1. p16 expression was also identified as an independent predictor of local recurrence and distant metastasis. Concerning p53 expression, it was significantly correlated with tumor size, site, risk category, mitotic index, local recurrence, distant metastasis, and the expression of p16, BCL2, and Cyclin D1. In contrast, BCL2 expression showed no significant association with most clinicopathological parameters, except for distant metastasis. However, it was significantly associated with the expression of p16, p53, and Cyclin D1. With respect to Cyclin D1 expression, it was significantly associated with tumor site, local recurrence, lymph node involvement, distant metastasis, and the expression of p16, p53, and BCL2. Regarding survival analysis, positive expression of p16 and p53 was significantly associated with shorter disease-free and overall survival. High BCL2 expression was correlated with reduced overall survival, whereas high Cyclin D1 expression showed a non-significant trend toward improved survival.

Conclusion

Our findings suggest that p16 and p53 expressions are valuable prognostic markers in GISTs, significantly associated with aggressive behavior and poor outcomes. p16 may serve as an independent predictor of recurrence and metastasis, while p53 could aid in risk stratification. Although BCL2 and Cyclin D1 showed associations with tumor aggressiveness, their prognostic roles remain uncertain. Further multicenter, standardized studies are needed to validate the clinical relevance of these markers.