Aberrant p53 Expression in Gastric Biopsies and Resection Specimens Following Neoadjuvant Chemoradiation: A Diagnostic Pitfall

Abstract

Gastric mucosal biopsies and resections from patients treated with neoadjuvant radiation and/or chemotherapy are frequently encountered. These samples may show histologic features related to therapy including inflammation, ulceration, and epithelial atypia. In some cases, epithelial atypia may be marked, prompting the use of adjunct p53 immunohistochemistry. We examined p53 expression by immunohistochemistry in gastric mucosa following therapy. We evaluated the histology and p53 immunohistochemical expression in gastric mucosa from 5 7 resections and 3 mucosal biopsies, from 60 patients treated with radiation and/or chemotherapy for gastroesophageal carcinoma (n  =  33) or pancreatic carcinoma (n  =  27). We identified histomorphologic features of therapy-related epithelial changes in 50 of 60 cases (83%). Abnormal p53 expression was present at least focally in nearly half the cases (27 of 60 cases; 45%), all of which showed morphologic evidence of therapy-related epithelial changes . Neuroendocrine cell micronests were present in 37 of 60 cases (62%). Next-generation sequencing (NGS) of foci with therapy-related epithelial changes showing abnormal p53 expression and carcinoma from the same patient was attempted and yielded results in 1 patient. Interestingly, differing TP53 alterations in the patient's adenocarcinoma and in a histologically benign esophageal submucosal gland with therapy-related epithelial changes and abnormal p53 expression were identified. Our results demonstrate that abnormal p53 expression is relatively common in gastric mucosal samples following radiation and/or chemotherapy and suggest that p53 expression should be avoided when distinguishing therapy -related changes from dysplasia or carcinoma. Furthermore, our NGS results raise interesting biological questions, which may warrant further investigation.