Loss of Menin Expression by Immunohistochemistry in Pancreatic Neuroendocrine Tumors: Comparison Between Primary and Metastatic Tumors

Objectives Molecular characterization of sporadic pancreatic neuroendocrine tumors (PanNETs) demonstrates frequent alterations in MEN1. As the role of menin immunohistochemistry as a potential biomarker is being developed, knowledge of whether the pattern of menin expression is the same in primary tumors and distant metastases may help in patient care. Therefore, we compared patterns of menin expression in matched primary tumors and metastases. Methods We evaluated loss of menin nuclear expression by immunohistochemistry in 44 matched samples of primary and metastatic PanNETs and concordance in staining pattern between primary and metastatic tumors. Results Menin nuclear expression was lost in 18 (41%) of 44 primary tumors and 17 (39%) of 44 metastases. Concordant loss of menin expression was observed in 41 cases (93%); discordance was observed in 3 cases (7%; 95% confidence interval, 1.4%-18.7%), including 2 with loss in the primary tumor but not the metastasis. Conclusions The concordance of menin staining between primary tumor and metastasis in most cases suggests that menin loss is an early event in PanNET tumorigenesis. The discordant expression observed in a small subset may be a source of menin-directed therapy failure; thus, repeat assessment of metastases may be helpful for treatment selection.