Expression and Prognostic Significance of Directed Therapy Targets and Mutational Analysis of the Egfr Pathway in Malignant Salivary Gland Tumors
Jerome F Cros, Helene Blons, Emilie Sbidian, Eric Tartour, Stephane Hans, Daniel Brasnu, Patrick Bruneval, Cecile Badoual. Georges Pompidou European Hospital, Paris, France; Paris Est Creteil University, Creteil, France; INSERM - Paris Descartes University, Paris, France
Background: Malignant salivary gland tumors are rare and pleomorphic entities (24 sub types, WHO 2005). Curative treatment relies on surgery sometimes completed by radiotherapy. Management of non-surgical, locally advanced or metastatic tumors is difficult as conventional chemotherapies are ineffective. Innovative treatments such as directed therapies may provide important benefits for these patients. The aim of this work was to assess the expression and prognostic value of directed therapy targets on salivary gland tumors and search for mutations within the key players of the EGFR pathway.
Design: Immunochemistry on formalin fixed paraffin embedded (FFPE) samples from 124 patients for c-KIT, EGFR, c-ERBB2, MUC1, phospho-mTOR, androgen/estrogens/progesterone receptors and Ki67 was performed and related to progression free interval and survival. DNA was extracted from FFPE sample and mutational status of EGFR/KRAS/ BRAF/HRAS were assessed.
Results: EGFR was the most expressed marker, found across almost all histotypes. Expression of the other markers was heterogeneous, depending on the tumor sub type. C-ERBB2, c-KIT and Ki67 were associated with the tumor grade. Tumor grade and a high proliferation index (Ki67>20%) were associated with the progression free interval and survival. None of the other marker was. No mutation was found in EGFR/KRAS/BRAF. 7% (7/104) of the tumors harbored a mutation at the codon 61 of HRAS. In epithelial and epithelial-myoépithélial carcinoma, the mutation rate reached 33%.
Conclusions: Several tumor subtypes expressed frequently some targets of directed therapies suggesting potential therapy leads. For instance, high levels of C-ERBB2 and androgen receptors in salivary duct carcinomas or C-KIT over expression in myoepithetial carcinomas were found. The EGFR pathway seems intact suggesting a low efficacy of small kinase inhibitors such as erlotinib or gefitinib. The mutation of H-RAS, known to be important but not sufficient to trigger urothelial carcinoma, calls for a broader screen to identify the pathways involved in malignant salivary gland tumors carcinogenesis.
Category: Head & Neck
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 161, Tuesday Afternoon