In situ expression patterns of melanoma-inhibiting activity (MIA) in melanomas and breast cancers

Abstract

Elevated levels of melanoma-inhibiting activity (MIA) were measured previously in the serum of patients with metastasized melanomas and in a subgroup of patients with advanced-stage breast cancers. This study aimed therefore to visualize in situ expression patterns of MIA protein and mRNA in melanomas and breast cancers by means of immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and in situ hybridization. Analysis of a panel of seven common melanocytic naevi, ten cutaneous melanomas, and 12 melanoma metastases detected high levels of both mRNA and protein in all melanomas and metastases, but only very low mRNA levels in three of seven naevi. Compared with the expression of pMel (HMB-45), tyrosine, and S-100 in these tumours, these results show that MIA provides a novel and sensitive marker for neoplastic melanocytes. Expression was not detected in other skin tumours including basal cell cancers and squamous cell cancers, nor in normal melanocytes and keratinocytes. MIA expression in adenocarcinomas was further studied in a panel of 20 specimens obtained from 16 advanced-stage breast cancers and four metastases. Significant levels of mRNA were detected in 17 of the 20 specimens and low levels in the other three tumours. Immunostaining visualized specific protein expression in the tumour cells of all 20 cancer specimens. These investigations define for the first time in situ expression patterns of MIA in melanomas and breast cancers and suggest a much broader expression in malignant epithelial neoplasms than previously determined by serum studies.