Molecular profile of salivary gland tumors: discovering new targets for therapy

Introduction. Due to variety of morphological subtypes and poor clinical response, comprehensive molecular profiling for salivary gland cancers become a part of treatment strategy for chemotherapy-resistant cases. Tumors of the salivary glands include more than 20 histological types distinguished by their biological characteristics, response to therapy, and prognosis. The search for specific therapeutically significant markers and mutations for various histological types of salivary gland tumors may allow the development of a diagnostic algorithm and improve patient treatment results.

Aim. To search for therapeutically significant molecular and genetic targets and immunohistochemical markers in various histological types of malignant salivary gland tumors.

Materials and methods. We analyzed data on 280 patients with unresectable recurrent and metastatic salivary gland cancer to identify the main characteristic therapeutically significant immunohistochemical (androgen receptor (AR), epidermal growth factor receptor type 2 (HER2neu), epidermal growth factor receptor (EgfR), programmed cell death receptor 1 (pD-L1) (CpS), сD117, estrogen receptor (ER), progesterone receptor (pR), pan-TRk) and molecular genetic targets (ALK, BRAF, ERBB2, KIT, MET, RET, ROS1, SMO, AR, HRAS, PIK3CA, PDGFRA, NTRK1-3) depending on the histological subtype of the tumor.

Results. Based on the results obtained, in comparison with previous studies, a greater diversity of therapeutically significant mutations, fusions and immunohistochemical markers was revealed for various histological types of tumors. Interestingly, increased expression of AR was detected not only in salivary duct carcinoma, but also in carcinoma ex pleomorphic adenoma, adenocarcinoma not otherwise specified, myoepithelial, mucoepidermoid, adenoid cystic, acinic cell, polymorphous adenocarcinomas. ETV6-NTRK3 gene fusions in addition to secretory carcinoma were detected in mucoepidermoid and salivary duct carcinomas. mutations and fusions in the RET gene have been identified in ductal and mucoepidermoid carcinomas, as well as adenocarcinoma not otherwise specified.

Conclusion. The results of the study allow to expand the group of patients for molecular genetic and IHC testing in order to individualize therapy.