Interconverted Phenotype Expression in Uveal Melanoma: Correlation with Clinicopathological Parameters

Abstract

Abstract: : Purpose: Pathology observational reports and experimental data suggest that co-expression of keratin and vimentin intermediate filaments "interconverted phenotype" in tumors confers a more aggressive phenotype. In this study we analyzed interconverted phenotypic expression in uveal melanomas and correlated with the known prognostic factors. Methods: Immunohistochemical staining with monoclonal antibodies to vimentin and cytokeratin 8/18 was performed on paraffin embedded tissues of 100 uveal melanomas and correlated with the cell types, the largest tumor diameter, mitosis, nuclear grade, pigmentation, tumor infiltrating lymphocytes and proliferation index Ki-67 (MiB1). Among the 100 tumors, 42 were spindle, 45 were mixed and 13 were epithelioid types. The tumors were divided in to 2 groups. Tumors with no extrascleral extension (n=81) and tumors with extrascleral extension (n=19). Results: Among the 100 tumors only vimentin positivity was seen in 82% tumors and only cytokeratin 8/18 positivity in 12% tumors. Interconverted phenotype positivity was seen in 12% tumors. Eighty-one(100%) of tumors with no extrascleral extension were negative for interconverted phenotype. Seven (36%) of 19 tumors with extrascleral extension had liver metastasis. Interconverted phenotype was positive in 5(71%) of 7 tumors with liver metastasis. Interconvered phenotype was positive in 5 mixed,6 epithelioid and 1 spindle cell melanoma. There was no correlation between Interconvered phenotype positivity and the known prognostic factors in uveal melanoma such as the largest tumor diameter, tumor infiltrating lymphocytes, mitosis, nuclear grade, pigmentation and proliferative activity by Ki- 67. Conclusions: Interconverted phenotype expression in the uveal melanoma by immunohistochemistry has prognostic significance. Further studies are needed to understand the biologic mechanisms of interconverted phenotype expression in uveal melanoma.

Keywords: cytoskeleton • immunohistochemistry • melanoma