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Updated: Apr 24, 2026
Implantation and Evaluation of Melanoma in the Murine Choroid via Optical Coherence Tomography
Published on: December 2, 2022
c-MET expression in primary and liver metastases in uveal melanoma
Faithlore P Gardner1, Daniel J Serie, Diva R Salomao
1aDivision 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.
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.
Insights
Uveal melanoma, a rare eye cancer, frequently expresses c-MET. Metastatic lesions show higher c-MET levels than primary tumors, suggesting c-MET inhibitors could be a promising therapy for this malignancy.
Area of Science:
- Oncology
- Molecular Pathology
- Ophthalmology
Background:
- Uveal melanoma (UM) is the most common primary intraocular malignancy in adults.
- Effective therapies for UM are urgently needed, particularly for metastatic disease.
- The c-MET pathway is implicated in various cancers and is a target for therapeutic inhibition.
Purpose of the Study:
- To investigate c-MET protein expression in primary and metastatic UM.
- To correlate c-MET expression with clinical and pathological variables in UM.
- To evaluate the potential of c-MET inhibitors as a therapeutic strategy for UM.
Main Methods:
- Retrospective analysis of UM tumor samples (primary and liver metastases) from 1990-2012.
- Immunohistochemistry used to assess c-MET expression.
- Quantification of c-MET expression via H-score by two pathologists.
Main Results:
- High c-MET expression observed in 98% of primary UM and 90% of liver metastases.
- Significant association between the percentage of positive cells and staining intensity of c-MET (P=0.007).
- Metastatic UM lesions exhibited significantly higher c-MET expression (median H-score 190) compared to primary tumors (median H-score 30, P=0.022).
Conclusions:
- c-MET is highly expressed in the majority of primary and metastatic UM.
- No association found between c-MET expression levels and clinicopathological features in this cohort.
- Elevated c-MET expression in metastases supports further investigation of c-MET inhibitors for UM treatment.
