Anomalous cytokeratin expression in malignant melanoma: one- and two-dimensional western blot analysis and immunohistochemical survey of 100 melanomas.

Immunohistochemical characterization is an accepted method of human cell typing and tumor diagnosis. The differentiation of undifferentiated carcinoma from amelanotic melanoma is usually achieved by demonstration of cytokeratin (CK) intermediate filaments in carcinoma but not in melanoma. In examination of 100 melanomas fixed in formalin or methacarn and frozen tissue sections, we have found CK-immunoreactivity in 2, 8, and 21% of cases, respectively, with multiple anticytokeratin antibodies displaying overlapping antigenic specificities. In addition, we have confirmed the anomalous expression of low molecular weight CK proteins by one- and two-dimensional gel electrophoresis and immunoblotting of extracts of an immunohistochemically positive case. This latter finding indicates that CK staining in melanomas reflects the presence of authentic CK peptides and is not an artefact induced by fixation or cross-reacting antibodies. These observations have direct implications for the application of immunohistochemistry to the present practice of diagnostic surgical pathology. The anomalous CK expression by melanoma limits the diagnostic reliability of immunohistochemically demonstrated CK alone to indicate a diagnosis of carcinoma, without the concomitant detection of additional tumor-associated antigens. The finding of anomalous CK expression only in metastatic or recurrent melanomas raises an interesting question of possible association with tumor progression.