GELATINASE-A EXPRESSION AND LOCALIZATION IN HUMAN BREAST CANCERS - ANIN-SITU HYBRIDIZATION STUDY AND IMMUNOHISTOCHEMICAL DETECTION USING CONFOCAL MICROSCOPY

The gelatinase A (72 kDa type IV collagenase) is a matrix metallo-prot einase which degrades basement membrane collagens. Various studies emp hasize its role in stromal invasion of cancers, but there is some cont roversy about its origin. Gelatinase A was localized by immunohistoche mistry using confocal microscopy in 15 human mammary carcinomas. In ad dition, the cells responsible for the synthesis of this enzyme were de tected by in situ hybridization. Most invasive and non-invasive tumour cells were labelled by immunohistochemistry. Of particular interest w as the pattern observed in some pre-invasive areas. Gelatinase A was f ound in fibroblasts in close contact with pre-invasive tumour clusters . Confocal observation allowed a more precise localization of gelatina se A to the periphery of tumour clusters along the basement membranes and in peritumour fibroblasts. The malignant epithelial cells were neg ative by immunohistochemistry in these areas. By in situ hybridization , mRNAs encoding gelatinase A were detected only in fibroblasts in clo se contact with pre-invasive and well differentiated tumour clusters. These findings support the hypothesis that peritumour fibroblasts prod uce gelatinase A and that breast cancer cells may bind this enzyme to their cell surface and/or internalize it.