Immunohistochemical expression and prognostic value of ER, PR and HER2/neu in pancreatic and small intestinal neuroendocrine tumors

Abstract

Background and aims: There has been limited study of estrogen and progesterone receptor (ER/PR) expression in gastrointestinal neuroendocrine tumors (GINETs) despite emerging evidence of hormone receptor regulation of pancreatic islet cells. Beta cells express PR and progesterone has been implicated in the pathogenesis of gestational diabetes. There is conflicting information regarding HER2/neu protein overexpression in GINETs. Investigation of ER, PR and HER2/neu expression in GINETs is therefore warranted.

Methods: A pathology database search identified 77 patients with primary pancreatic (40) or small intestinal (37) NETs diagnosed from 1991 to 2009. Ki67, ER, PR and HER2/neu were assessed via immunohistochemistry. ER and PR were interpreted as negative (0), 1+ (Allred score 3-7/8) or 2+ (Allred score 8/8), and HER2/neu was assessed according to ASCO/CAP guidelines for breast carcinoma. Clinical correlation and survival outcomes were ascertained by a retrospective clinical chart review.

Results: 2+ PR staining was observed more often in pancreatic compared to small intestinal cases (55 vs. 8%; p < 0.001). All small intestinal NETs with 2+ PR were duodenal primaries. Cases with 2+ PR presented significantly less often with nodal or distant metastases compared to cases with 0/1+ PR (13 vs. 61.5%; p < 0.001) and had significantly improved disease-free survival (median 155 vs. 38 months; p = 0.037). Only one case demonstrated 2+ ER staining and all were negative for HER2/neu.

Conclusion: GINETs with strong (2+) PR expression are associated with pancreatic/duodenal origin, lower stage disease, and more favorable clinical prognosis. Further study is needed to determine the clinical utility of PR expression in GINETs.