AMPLIFICATION AND OVEREXPRESSION OF HER-2 NEU IN CARCINOMAS OF THE SALIVARY-GLAND - CORRELATION WITH POOR-PROGNOSIS/

There are few reliable prognostic markers of biological aggressiveness for head and neck carcinomas in general. For salivary gland carcinoma s, anatomic location, tumor size, histological grade, and extent of di sease involvement are considered to be clinically important risk facto rs for recurrent disease. Molecular genetic alterations in salivary gl and carcinomas have not been characterized, and tumor cell proteins ha ve not been shown to be prognostically significant. Here a cohort of m ucoepidermoid carcinomas of the major (parotid and submandibular) sali vary 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. Archival tiss ues resected from 58 patients with mucoepidermoid carcinoma of salivar y glands were evaluated for HER-2/neu gene amplification by fluorescen ce in situ hybridization and for gene expression by immunohistochemist ry in a blinded fashion. Clinical follow-up information was compared w ith the results of these analyses to determine whether there were sign ificant associations. Overexpression, identified as membrane immunosta ining by immunohistochemistry, was observed in 22 of 58 (38%) mucoepid ermoid carcinomas. Gene amplification, characterized by fluorescence i n situ hybridization, was observed in 12 (21%) cases. Eleven of the 12 cases with gene amplification were also immunostained for HER-2/neu. Both gene amplification (P = 0.0001, P < 0.0001) and immunostaining (P < 0.0001, P < 0.0001) were correlated with shorter disease-free inter val and poorer overall patient survival, respectively. Multivariate an alysis showed that HER-2/neu immunostaining and amplification were mar kers of poor prognosis independent of histopathological grade, tumor s ize, and involvement of regional lymph nodes. HER-2/neu is amplified a nd/or overexpressed in approximately one-third of mucoepidermoid carci nomas of salivary glands. Amplification and/or overexpression appears to be an independent marker of poor prognosis in mucoepidermoid carcin omas of the salivary glands as it is in carcinomas of the breast, ovar y, and endometrium.