Molecular Pathology of Salivary Gland Neoplasms: Diagnostic, Prognostic, and Predictive Perspective

Abstract

Salivary gland neoplasms are an uncommon and widely heterogeneous group of tumors. In recent years, there has been considerable progress in efforts to reveal the molecular landscape of these tumors, although it is still limited and appears to be only the tip of the iceberg. Genomic aberrations, especially specific chromosomal rearrangements including CRTC1-MAML2 and CRTC3-MAML2 in mucoepidermoid carcinoma, MYB-NFIB and MYBL1-NFIB fusions in adenoid cystic carcinoma, PLAG1 and HMGA2 alterations in pleomorphic adenoma and carcinoma ex pleomorphic adenoma, ETV6-NTRK3 and ETV6-RET in secretory carcinoma, EWSR1-ATF1 and EWSR1-CREM in clear cell carcinoma, provide new insights into the molecular pathogenesis of various salivary gland neoplasms and help to better classify them. These genetic aberrations primarily serve as diagnostic tools in salivary gland tumor diagnosis; however, some also have promise as prognostic or predictive biomarkers. This review summarizes the latest developments in molecular pathology of salivary gland tumors with a focus on distinctive molecular characteristics.

Expression of Transcription Factor CREM in Human Tissues

“…21 EWSR1-CREM gene fusions have recently been found in several types of tumors. 9–13 We wanted to test whether the baseline expression of CREM in normal tissues would be low enough for the detection of overexpression of a fusion protein. The antibody readily detected an EWSR1-CREM fusion protein in Western blotting of a melanoma cell line, and IHC in an MEC with EWSR1-CREM fusion gene was positive.…”

“…It is recurrent in several types of neoplasia such as mesenchymal tumors, in hyalinizing clear cell carcinoma of salivary glands, and, most recently, in a malignant epithelioid neoplasm with predilection for mesothelial-lined cavities. [9][10][11][12][13] The EWSR1-CREM fusion genes encode fusion proteins with an N-terminal EWSR1 transactivation domain and a C-terminal DNA-binding domain of CREM. 14 Detection of the fusion protein or neoexpression of the CREM protein could potentially serve as a surrogate for genetic testing, if the expression of wild-type CREM protein in tissues would be low.…”

“…It is recurrent in several types of neoplasia such as mesenchymal tumors, in hyalinizing clear cell carcinoma of salivary glands, and, most recently, in a malignant epithelioid neoplasm with predilection for mesothelial-lined cavities. 9–13 The EWSR1-CREM fusion genes encode fusion proteins with an N-terminal EWSR1 transactivation domain and a C-terminal DNA-binding domain of CREM. 14…”

An Overview on the Histogenesis and Morphogenesis of Salivary Gland Neoplasms and Evolving Diagnostic Approaches

“…All SGN have certain genetic alterations that can be categorized, as in Table 4, according to their role in diagnosis, prediction, and prognosis. [47]. While traditional diagnostic methods have been successful, a clearer understanding in the cellular and molecular mechanisms of SGN is necessary.…”

ETV6-NTRK3 translocation-associated low-grade mucinous bronchial adenocarcinoma: A novel bronchial salivary gland-type non-small cell lung cancer subtype

“…3J), which can promote cell proliferation and survival through the activation of the Ras-MAP kinase and PI3K-Akt pathways. NTRK3 fusions are relatively common in salivary gland tumors, with a frequency of 5% in a recent large pan-cancer study [13], and ETV6-NTRK3 fusions having been found in both secretory carcinoma (common, >95 %) and salivary duct carcinoma (rare) [14]. Secretory carcinoma (SC) (previously known as 'mammary analog secretory carcinoma' (MASC)) is a low-grade, salivary gland carcinoma.…”