Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer (SGC). Activation of the cellular MET (c-MET) receptor tyrosine kinase has been implicated in cell proliferation, survival, migration, and invasion. The aim of this study was to evaluate the frequency of MET overexpression and its correlation to clinicopathological factors in SDC.
136 patients were collected by a retrospective search of the Nationwide Network and Registry of Histo- and Cytopathology (PALGA) in the Netherlands. Formalin-fixed paraffin-embedded tumor blocks and hematoxylin and eosin stained slides were requested for pathological review. MET expression was evaluated by immunohistochemical staining on primary tumors. These data were correlated to clinicopathological factors.
c-MET was positive in 54 of 136 tumors (39.7%). Of these 54 tumors, 50 had a cytoplasmic staining pattern and 23 had a membranous staining pattern, so in 19 tumors both cytoplasmic and membranous staining was observed. No correlations were found between cytoplasmic or membranous MET and high stage disease (stage 3 and 4 versus stage 1 and 2, p = 0.606 and p = 0.300 respectively), number of positive lymph nodes (p = 0.263 and p = 0.955 respectively), lymph node ratio (p = 0.192 and p = 0.771 respectively), androgen receptor-status (p = 0.858 and p = 0.258 respectively), HER2-status (p = 0.257 and p = 0.595 respectively), time to recurrence (p = 0.559 and p = 0.959 respectively), time to distant metastases (p = 0.398 and p = 0.666 respectively), or overall survival (p = 0.754 and p = 0.516 respectively). Membranous MET staining occurred more frequently in SDC ex pleomorphic adenoma (14 of 52 tumors) than in the ‘de novo’ SDC (9 of 84 tumors) (p = 0.014). In SDC ex pleomorphic adenoma we also found more HER2-positive tumors (p = 0.041).
Cytoplasmic and membranous MET are overexpressed in SDC and may be a target for MET-targeted therapy. It is not a prognostic factor for overall survival, possibly because frankly invasive SGCs often show less receptor expression then minimally invasive SGCs or pleomorphic adenomas. The higher expression of c-MET and HER-2 in SDC ex pleomorphic adenoma needs further investigation.
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Carla M.L. van Herpen
All authors have declared no conflicts of interest.