These results suggest that HER2 or EGFR gene abnormality could play an important role in the development of high-grade MEC, and also in the progression from MAML2 fusion-positive low-/intermediate-grade to high-grade in a subset of MEC.
Several therapy leads were identified, including high levels of HER2 and androgen receptors in salivary duct carcinomas, C-KIT in myoepithelial carcinomas and EGFR in mucoepidermoid carcinomas.
Consequently, different signaling cascades were found activated: (1) an EGFR/HER2(-Akt)-mTOR-dependent axis, with gene gains of HER2 and/or EGFR, activated in salivary duct carcinoma and carcinoma ex pleomorphic adenoma; (2) an EGFR(-Akt)-mTOR-dependent pathway activated in mucoepidermoid carcinoma or acinic cell carcinoma, without HER2 or EGFR gene alterations; and (3) an Akt-dependent pathway without EGFR/HER2 activation in other types.
HER2 was overexpressed in 34 of 319 (10.65%) mucoepidermoid carcinomas, one of 170 (0.59%) acinic cell adenocarcinomas and three of 14 (21.43%) salivary duct carcinomas.
Archival tissue sections of 22 MEC and 6 ACC tumors of the major salivary glands were evaluated immunohistochemically for expression of erbB-2, erbB-3, EGRF, and TGF-alpha.
The histopathological characteristics, proto-oncogene amplification, immunohistopathology of the c-erbB-2 product distribution, and the DNA content of nuclei were examined in metastatic brain tumors, which consisted of seven adenocarcinomas, a large cell carcinoma, a squamous cell carcinoma, a renal cell carcinoma and a mucoepidermoid carcinoma.
The c-erbB-2 expression as measured by grain counts per cell for the pleomorphic adenomas (16.29 +/- 1.87; 95% CI), mucoepidermoid carcinomas (31.52 +/- 0.08; 95% CI) and the acinic cell carcinomas (44.24 +/- 17.11; 95% CI) were significantly greater than the expression for the normal group.
Here a cohort of mucoepidermoid carcinomas of the major (parotid and submandibular) salivary glands are analyzed for a molecular genetic alteration, HER-2/neu gene amplification, and gene amplification and expression results are compared with long-term clinical follow-up information.