Elsevier

Oral Oncology

Volume 45, Issue 11, November 2009, Pages 986-990
Oral Oncology

Treatment relevant target immunophenotyping of 139 salivary gland carcinomas (SGCs)

https://doi.org/10.1016/j.oraloncology.2009.05.635Get rights and content

Summary

Salivary gland carcinomas (SGCs) are rare tumors encompassing a wide spectrum of histologic/biologic entities. Standard non-surgical treatments are ineffective in case of advanced disease. Our aim was to analyze SGCs deregulation gene profiles that could become target for innovative treatment options.

Samples from 139 patients with primary, recurrent and/or metastatic SGCs were investigated by immunohistochemistry for protein encoded by tyrosine kinases receptors (TKRs) i.e. c-kit, HER2, EGFR and hormonal receptors, i.e. androgen (AR), estrogen (ER) and progesterone receptors (PgR). In 26 cases, the HER2 immunohistochemical analysis was complemented by fluorescence in-situ hybridization analysis.

EGFR was the most expressed TKRs (71%) and it was found across all histotypes.

c-Kit expression was mainly restricted to adenoid cystic carcinoma (78%) while HER2 expression, mostly sustained by gene amplification, correlated with salivary duct carcinoma (SDC) in 44% of cases and adenocarcinoma, not otherwise specified (AD, NOS) in 21% of cases. With respect to histogenetic classification, TKRs expression occurred more often in tumors derived from intercalated duct rather than excretory ones with the only exception of HER2. AR was found in 13% of samples, restricted to SDC and AD, NOS and it was co-expressed with HER2 in more than half of the SDC cases. ER and PgR positivity was never detected.

This TK-hormonal receptors analysis identify a histotype-specific profiles that could be exploited for better selecting patients for innovative treatment within prospective studies.

Introduction

Salivary gland carcinomas (SGCs) are a rare group of malignant tumors, comprising a spectrum of variable morphologic, immunophenotypic and biologic entities1 updated in terms of pathology and genetics by the WHO classification.2 According to the histogenetic classification approach and aware that histologic similarity does not necessarily imply that a particular tumor arises from the structure that it mimics, adenoid cystic carcinoma and malignant myoepithelioma develop from intercalated duct and salivary duct carcinoma and mucoepidermoid carcinoma from excretory duct. To which extent SGCs histology and their similarities to epithelial gland structures contribute to clinically define a specific entity, is difficult to say. Notably, in terms of prognosis, the histogenetic classification postulates that carcinomas with myoepithelial participation are biologically low-grade (adenoid cystic, myoepithelial) while whose devoid of myoepithelium (salivary duct, adenocarcinoma, mucoepidermoid) high-grade.3 In this context, the identification of molecular-based histotype-specific objective markers might contribute to the subjective phenotypic evaluation in the diagnosis, by improving understanding of single tumor, and more importantly it might help for biologic tumor screening in which targeted therapy might be investigated.

To our best knowledge, the present study is the largest series of SGCs, in which tyrosine kinase receptors (TKRs) and hormonal receptors (HRs) expression were systematically investigated.

Section snippets

Patients and samples

One hundred and thirty nine patients with recurrent and/or metastatic SGC, origining from the major or minor salivary glands, who were consecutively admitted to the Head and Neck Medical Oncology Unit of our institute over a period of 5 years (from 1999 to 2004), were retrospectively analyzed for the presence in immunohistochemistry of c-kit, HER2, EGFR together with androgen receptor (AR) and estrogen/progesteron receptors (ER/PgRs). In all cases, histopathologic diagnosis was reviewed and

Case material

According to the WHO classification the case material consisted of: 63 adenoid cystic carcinomas (ACC), 26 salivary duct carcinomas (SDC), 26 adenocarcinomas, not otherwise specified (AD, NOS), five myoepithelial carcinomas (MC), five high grade (HG) mucoepidermoid carcinomas (MEC), four poorly differentiated carcinomas (PDC) and 10 other histotypes, including two acinic cell carcinomas, one clear cell carcinoma, two papillary cistoadenocarcinomas; three basal cell adenocarcinomas and two

Discussion

This is the largest series of SGCs, in which an immunohistochemical profile based on gene products relevant for possible target treatments has been systematically performed. Considering the histotypes, c-kit occurred in cases of ACC, HER2 in cases of SDC and in AD, NOS, while EGFR was found across all histotypes. If histogenenesis is taken into account, with the exception of HER2 characteristically seen in tumors of excretory type, TKRs expression was mainly associated with tumors of

Conflict of Interest Statement

Lisa Licitra, MD has served as Advisory Board Member for Amgen, Eli Lilly, Glaxo Smith Kline, and Merck Serono.

Acknowledgement

Supported in part by Associazione Italiana per la Ricerca sul Cancro, Milan, Italy.

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