Salivary Duct Carcinoma – Altered Pathways for Targeted Therapy
Chandrani Chattopadhyay, Michael E Kupferman, Merrill S Kies, Michelle D Williams. UT MD Anderson Cancer Center, Houston, TX
Background: Salivary duct carcinoma (SDC) is a high grade adenocarcinoma with median survival of less than three years. Identifying targetable pathways are needed for improved outcomes in this aggressive disease. Novel inhibitors of PI3K currently in clinical trials attempt to suppress misregulation which may be caused by loss of Phosphatase and tensin homolog (PTEN) expression, a tumor suppressor gene. Whereas direct inhibitors of c-MET, a proto-oncogene associated with motility, and proliferation, are also being studied which actives multiple pathways including that of PI3K. As little is known regarding these potential targetable pathways in salivary duct carcinoma, we sought to define their incidence and correlate with clinical parameters.
Design: A tissue microarray composed of formalin-fixed paraffin embedded tumor tissue from 62 salivary duct carcinomas formed the study cohort. Immunohistochemical analysis was performed for PTEN, c-MET and p-MET expression using standard techniques (PTEN 6H2.1, 1:100, Dako, Carpenteria, CA; c-MET, sc-10, 1:200, Santa Cruz). Each tumor was evaluated for expression in duplicate cores for: PTEN expression- negative or positive (cytoplasm and/or nuclear) and c-MET/ p-MET as 0 (no expression), 1+ (weak), 2+ (moderate) and 3+ (strong) staining.
Results: Within the 62 SDCs, PTEN loss of expression was seen in 22 (34%), a similar incidence as seen in breast adenocarcinoma. C-MET showed high (2 or 3+) expression in 31(50%) of the SDCs and high p-MET expression was present in 27(43%) tumors. High-p-MET occurred in SDCs with all ranges of c-MET expression (0-3+). No correlation was noted between clinical outcome and any of the markers analyzed.
Conclusions: Alterations in PTEN and MET expression occur in over a third of salivary duct carcinomas and may allow for targeted therapies through inhibition of the PI3K pathway and MET directly. Studies are on-going to delineate the molecular basis for these alterations.
Category: Head & Neck
Monday, March 19, 2012 2:45 PM
Platform Session: Section F, Monday Afternoon