text: Treatment relevant target immunophenotyping of 139 salivary gland carcinomas (SGCs).
  Salivary gland carcinomas (SGCs) are rare tumors encompassing a wide spectrum of histologic/biologic entities. Standard non-surgical treatments are ineffective in case of advanced disease. Our aim was to analyze SGCs deregulation gene profiles that could become target for innovative treatment options. Samples from 139 patients with primary, recurrent and/or metastatic SGCs were investigated by immunohistochemistry for protein encoded by tyrosine kinases receptors (TKRs) i.e. c-kit, HER2, EGFR and hormonal receptors, i.e. androgen (AR), estrogen (ER) and progesterone receptors (PgR). In 26 cases, the HER2 immunohistochemical analysis was complemented by fluorescence in-situ hybridization analysis. EGFR was the most expressed TKRs (71%) and it was found across all histotypes. c-Kit expression was mainly restricted to adenoid cystic carcinoma (78%) while HER2 expression, mostly sustained by gene amplification, correlated with salivary duct carcinoma (SDC) in 44% of cases and adenocarcinoma, not otherwise specified (AD, NOS) in 21% of cases. With respect to histogenetic classification, TKRs expression occurred more often in tumors derived from intercalated duct rather than excretory ones with the only exception of HER2. AR was found in 13% of samples, restricted to SDC and AD, NOS and it was co-expressed with HER2 in more than half of the SDC cases. ER and PgR positivity was never detected. This TK-hormonal receptors analysis identify a histotype-specific profiles that could be exploited for better selecting patients for innovative treatment within prospective studies.