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Amplification and Overexpression of HER-2/neu in Carcinomas of the Salivary Gland: Correlation with Poor Prognosis¹

Departments of Pathology [M. F. P., G. H., J. Y. Z., Y. M.] and Preventive Medicine [M. C. P.], University of Southern California School of Medicine, Los Angeles, California 90033; Division of Research and Development, Oncor, Inc., Gaithersburg, Maryland 20877 [J. G., J. D-B., W. J.]; Division of Hematology and Oncology, University of California Los Angeles School of Medicine, Los Angeles, California 90024 [D. J. S.]; and Department of Pathology, M.D. Anderson Cancer Center, University of Texas, Houston, Texas 77030 [J. G. B., A. K. E-N.]

There are few reliable prognostic markers of biological aggressiveness for head and neck carcinomas in general. For salivary gland carcinomas, anatomic location, tumor size, histological grade, and extent of disease involvement are considered to be clinically important risk factors for recurrent disease. Molecular genetic alterations in salivary gland carcinomas have not been characterized, and tumor cell proteins have not been shown to be prognostically significant. 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.

Archival tissues resected from 58 patients with mucoepidermoid carcinoma of salivary glands were evaluated for HER-2/neu gene amplification by fluorescence in situ hybridization and for gene expression by immunohistochemistry in a blinded fashion. Clinical follow-up information was compared with the results of these analyses to determine whether there were significant associations.

Overexpression, identified as membrane immunostaining by immunohistochemistry, was observed in 22 of 58 (38%) mucoepidermoid carcinomas. Gene amplification, characterized by fluorescence in 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 interval and poorer overall patient survival, respectively. Multivariate analysis showed that HER-2/neu immunostaining and amplification were markers of poor prognosis independent of histopathological grade, tumor size, and involvement of regional lymph nodes.

HER-2/neu is amplified and/or overexpressed in approximately one-third of mucoepidermoid carcinomas of salivary glands. Amplification and/or overexpression appears to be an independent marker of poor prognosis in mucoepidermoid carcinomas of the salivary glands as it is in carcinomas of the breast, ovary, and endometrium.

¹ Supported in part by National Cancer Institute Grants CA48780 and CA50589, and Molecular Core Laboratory Facilities of the General Clinical Research Centers provided by NIH/National Center for Research Resources/General Clinical Research Centers Grant MO1 RR-43.

² To whom requests for reprints should be addressed, at Department of Pathology—HMR910, University of Southern California School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033.

Received 4/25/94. Accepted 9/ 2/94.

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