Frequency and pattern of p16 expression in neuroendocrine neoplasms

Abstract

ABSTRACT Objectives: To determine the frequency and pattern of p16 expression in neuroendocrine neoplasms and evaluate its association with tumor types and grades. Methodology: This prospective descriptive study was conducted at the Department of Histopathology, Shifa International Hospital, Islamabad, from November 2024 to October 2025. A total of 85 cases of NENs were included using a non-probability consecutive sampling technique. Formalin-fixed paraffin-embedded tissue sections were evaluated using immunohistochemistry for p16 expression. Clinicopathological variables including age, gender, tumor site, subtype, and grade were recorded. Data were analyzed using SPSS version 27.0, and associations were assessed using the chi-square test, with p<0.05 considered statistically significant. Results: The mean age was 55.8±14.66 years, with male predominance in 56.5% (48) cases. Well-differentiated neuroendocrine tumors comprised 69.4% (59) of cases, while neuroendocrine carcinomas accounted for 30.6% (26). The liver was the most common site in 29.4% (25) cases. Diffuse p16 positivity was observed in 24.7% (21) cases, heterogeneous positivity in 32.9% (28), and negative staining in 42.4% (36). Diffuse p16 expression was significantly more frequent in neuroendocrine carcinomas than in well-differentiated neuroendocrine tumors [65.4% (17) vs. 6.8% (4), p < 0.001], with an odds ratio of 25.97 (95% CI: 7.10–95.05). Conclusion: Diffuse p16 expression was significantly more frequent in neuroendocrine carcinomas than in well-differentiated neuroendocrine tumors, while heterogeneous and negative p16 expression predominated in well-differentiated tumors. p16 immunohistochemistry may serve as a useful adjunct in distinguishing neuroendocrine carcinomas from Grade-3 well-differentiated neuroendocrine tumors in diagnostically challenging cases.