title: c-MET expression in primary and liver metastases in uveal melanoma.
abstract: There is a pressing need for effective therapies to treat uveal melanoma. Agents that inhibit the c-MET pathway have shown promise in multiple malignancies that overexpress c-MET. Herein, we assess c-MET expression in both primary uveal melanoma and liver metastases of uveal melanoma and evaluate the association of c-MET expression with clinical and pathologic variables. We have retrospectively identified tumor samples from primary and liver metastases of uveal melanoma from 1 January 1990 to 1 January 2012. We utilized immunohistochemistry to assess c-MET expression, and two pathologists quantified c-MET expression using an H-score (product of the intensity of staining and percentage of positive cells). The Mann-Whitney U-test, Pearson's correlation, and Cox model were used as appropriate. Thirty-nine of 40 (98%) primary tumors and nine of 10 (90%) metastatic liver lesions expressed c-MET (H-score range 0-300). There was a strong association between the percentage of positive cells and the intensity of c-MET expression (P=0.007). We found no association between c-MET H-score and clinicopathologic variables such as age, sex, or stage. c-MET expression was significantly higher in metastatic compared with primary tumors (median H-score 190 vs. 30, P=0.022). c-MET is expressed in the vast majority of primary and liver metastases of uveal melanomas; however, c-MET expression did not associate with pathologic features in our cohort. Metastatic lesions have higher expression of c-MET expression than primary tumors. Clinical trials involving c-MET inhibitors deserve further study in patients with uveal melanoma in both the adjuvant and metastatic setting.
authors.affiliation: aDivision of Hematology/Oncology bDepartment of Biomedical Informatics and Biostatics cDepartment of Pathology, Mayo Clinic Florida, Jacksonville, Florida dDepartment of Pathology eDepartment of Medical Oncology fDepartment of Ophthalmology, Mayo Clinic Rochester, Rochester, MN, USA.
authors.forename: Faithlore P
authors.initials: FP
authors.lastname: Gardner
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Serie
authors.forename: Diva R
authors.initials: DR
authors.lastname: Salomao
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Wu
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
authors.forename: Jose S
authors.initials: JS
authors.lastname: Pulido
authors.forename: Richard W
authors.initials: RW
authors.lastname: Joseph
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012189:Retrospective Studies; D014604:Uveal Neoplasms / Q000473:pathology*; D000098943:Uveal Melanoma
chemical_list: D014408:Biomarkers, Tumor; D019859:Proto-Oncogene Proteins c-met