Colorectal Adenocarcinomas with Positive Immunohistochemical NET Features: A Descriptive Study of Their Clinical Behavior

Abstract

Introduction: Colorectal cancer is a major health problem. Neuroendocrine differentiation in prostate adenocarcinoma has been associated with poor prognosis and tumor progression. We previously showed that neuroendocrine tumor (NET) cells exist in a subset of colorectal adenocarcinomas. NETs contain bioactive amines and peptides, which may promote the tumor growth. We abstracted clinical data from the subset of colorectal adenocarcinomas with NET cells. Our aim is to characterize the clinical behavior of colorectal adenocarcinomas with immunohistochemical NET features. Methods: The study was approved by the VA IRB. We randomly selected 40 paraffin-embedded colon adenocarcinoma tissue sections of varied stage and grade from archival tissues (2012-2014). One pathologist, blinded to the tumor grade and extent of disease, reviewed all slides. Archival blocks were sectioned and haematoxylin and eosin (H&E), chromogranin A (CGA) and synaptophysin (Syn) immunohistochemistry staining were done. For the patients with colorectal cancers with immunohistochemical NET features, we reviewed patient charts for age, tumor stage at cancer diagnosis, mortality, BMI at diagnosis, and most recent LDL checked before the diagnosis. Results: Of 40 specimens, 13/40 (33%) had NET features by H&E. Of 13 specimens, 9 cases were positive for at least one NET biomarker. A total of 6/13 (46%) colorectal cancers with positive NET features stained positive for both CGA and Syn. Of 9 specimens that stained positive for at least one NET marker, average patient age at diagnosis was 66 years old. Three patients (33%) had regional positive nodes on the resected specimen at the time of diagnosis. Three patients (33%) had tumor stage 1, two patients (22%) had tumor stage 2, two patients (22%) had tumor stage 3, and two patients (22%) had tumor stage 4. Two patients (22%), one with tumor stage 3 and one with tumor stage 4 at diagnosis, died. For the 9 patients, average BMI at diagnosis was 32. The average total cholesterol was 166 and the average LDL was 99. Conclusion: This is the first study to evaluate the clinical behavior of colorectal adenocarcinomas with the presence of NETs. Our study involved a small number of patients with colorectal cancer with positive NET biomarkers. Further investigations to compare colorectal adenocarcinomas with and without NET biomarkers should be done in the future to evaluate whether positive NET biomarkers predict more aggressive disease.