Immunohistochemical expression of retinoblastoma protein in cutaneous melanomas.

Abstract

Retinoblastoma protein (pRB) is the product of a tumour-suppressor gene (rb) mapped to chromosome 13q14. pRB acts as a control checkpoint at the G1 phase of the cell cycle, preventing cells from entering into the S phase. Mutational inactivation of both normal alleles leads to loss of pRB expression and the development of malignant neoplasms. Absence of pRB occurs in retinoblastomas, sarcomas and several other types of tumours. The potential role of pRB in the pathogenesis of cutaneous melanoma is unknown, and was the subject of this investigation. Formalin-fixed, paraffin-embedded sections of four cutaneous melanoma metastases, 17 primary invasive melanomas and 10 predominantly intradermal melanocytic naevi were studied. Monoclonal antibodies directed against pRB and Ki-67 antigen were used after microwave heating of sections to restore antigenicity. pRB was not detected in morphologically normal epidermal melanocytes. In five naevi, only scattered cells (1%) expressed pRB, whereas in the other five naevi, pRB expression was undetectable. In contrast, pRB was detected in all primary and metastatic melanomas (5-70% of cells). Expression was always localized to nuclei. Ki-67 expression was detected only in the melanomas, with both cellular staining and regional localization similar to that shown by pRB in 13 of the 20 melanomas studied with both antibodies. pRB appears to be expressed at higher levels in melanomas than in benign naevi. It therefore seems unlikely that loss of rb expression is an important factor in the pathogenesis of melanoma.