Syntaxin 1: A Novel Robust Immunophenotypic Marker of Neuroendocrine Tumors

Considering the specific clinical management of neuroendocrine (NE) neoplasms (NENs), immunohistochemistry (IHC) is required to confirm their diagnosis. Nowadays, synaptophysin (SYP), chromogranin A (CHGA), and CD56 are the most frequently used NE immunohistochemical markers; however, their sensitivity and specificity are less than optimal. Syntaxin 1 (STX1) is a member of a membrane-integrated protein family involved in neuromediator release, and its expression has been reported to be restricted to neuronal and NE tissues. In this study, we evaluated STX1 as an immunohistochemical marker of NE differentiation. STX1, SYP, CHGA, and CD56 expression was analyzed in a diverse series of NE tumors (NETs), NE carcinomas (NECs), and non-NE tumors. All but one (64/65; 98%) NETs and all (54/54; 100%) NECs revealed STX1 positivity in at least 50% of the tumor cells. STX1 showed the highest sensitivity both in NETs (99%) and NECs (100%) compared to CHGA (98% and 91%), SYP (96% and 89%), and CD56 (70% and 93%), respectively. A wide variety of non-NE tumors were tested and found to be uniformly negative, yielding a perfect specificity. We established that STX1 is a robust NE marker with an outstanding sensitivity and specificity. Its expression is independent of the site and grade of the NENs.