Analysis and significance of c-MET expression in adenoid cystic carcinoma of the salivary gland.
Adenoid cystic carcinoma (ACC), a rare salivary gland malignancy, is a histogenetic, morphologic, and clinical heterogeneous disease. Extensive efforts have been made to characterize molecular events associated with these tumors, including the identification of prognostic and predictive biomarkers. Increased copy number gain and amplification of c-Met, the cell surface receptor for hepatocyte growth factor, has been shown to enhance tumor growth and invasiveness and promote metastasis in certain tumor types. In this study, we evaluated the expression of c-Met by immunohistochemistry (IHC) in a large cohort of salivary gland ACCs and examined its clinicopathologic implications. Archival formalin-fixed paraffin-embedded blocks from 200 ACC patients were used in this study. Pathologic patterns and phenotypic expression of c-Met were recorded and compared with clinical factors including gender, age, disease stage at diagnosis, and clinical outcomes. Correlations between c-MET expression and clinical characteristics were assessed by Pearson's chi-square test or by the 2-tailed Fisher exact test. Curves describing overall survival were generated by Kaplan-Meier product limit method. Strong c-MET expression was seen in inner ductal and outer myoepithelial cells in 53.2% of the cases. There was no correlation between c-Met overexpression and clinicopathologic parameters or patient's overall survival ( p = .94074). In conclusion, c-MET expression is high in a significant subgroup of ACC patients. While c-MET expression is not a prognostic factor in ACC, its role as a predictive marker of benefit from MET inhibitors deserves further investigation.
a Department of Pathology ; The University of Texas MD Anderson Cancer Center ; Houston , TX USA.
Diana
D
Bell
Renata
R
Ferrarotto
Melanie D
MD
Fox
Dianna
D
Roberts
Ehab Y
EY
Hanna
Randal S
RS
Weber
Adel K
AK
El-Naggar
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D055815:Young Adult
D014408:Biomarkers, Tumor; D019859:Proto-Oncogene Proteins c-met
adenoid cystic carcinoma; c-Met; salivary; targeted therapy