Metastatic human melanoma. Phenotypic heterogeneity and antigen expression in relation to the clinical status.

According to animal experiments, metastasis to a particular organ depends on the phenotype of the tumor cells. Widespread metastatic dissemination including internal organs would therefore, at least in part, depend on the capacity of tumor cells to modulate, resulting in increased phenotypic heterogeneity. We found evidence for this assumption in human melanoma by phenotyping metastases (mainly cutaneous/subcutaneous) from 59 patients by the use of six monoclonal antibodies. Interlesional antigenic heterogeneity was present in 22/33 (67%) patients with disseminated metastases including at least one internal organ, but only in 4/26 (15%) patients whose metastases were restricted to skin and/or skin-draining lymph nodes (P less than or equal to 0.01). Chemotherapy cannot be the main reason for interlesional phenotypic heterogeneity, as seen by comparison of treated and untreated patients. Aneuploid melanoma metastases, as an indication for instability on the chromosomal level, were found in the majority of patients (84%) regardless of their clinical situation. Widespread disease was significantly related to the loss of the cytoplasmatic antigen K-1-2 and to the expression of the 130-kDa membrane antigen A-1-43.