Matrix metalloproteinase 2 immunoreactive protein appears early in cervical epithelial dedifferentiation

Objective. Expression of the immunoreactive protein of matrix metalloprotei nase 2 (MMP-2) was studied in cervical tumors representing various stages o f cell atypia and differentiation. In this study, we evaluated whether the expression of MMP-2 is an early or late event in the process of dedifferent iation and cancer progression. Methods. Paraffin tissue sections from 60 cervical neoplasias including 38 cervical intraepithelial neoplasias (CINs) and 22 early-stage (stage IB and IIA) squamous cervical carcinomas were studied with respect to the express ion of MMP-2 protein by using immunoperoxidase staining. Results. The staining pattern of MMP-2 in the CIN lesions usually differed from that in squamous carcinoma. Latent MMP-2 protein localized, in most of the cases, to the periphery of the CIN cells, but was diffuse in the cytop lasm of the carcinoma cells. No correlation was found between overexpressio n of MMP-2 protein and degree of dysplasia, nor was there any association b etween MMP-2 and human papillomavirus (HPV). High scores for MMP-2 were obs erved only in histologically higher-grade early-stage cervical carcinomas. The lymph node metastases derived from high-MMP-2-score primary tumors were also positive for MMP-2. No correlation between MMP-2 staining and clinica l course or prognosis was found. Conclusions. MMP-2 expression is an early event during dedifferentiation an d malignant transformation in cervical neoplasias. The pattern of staining is different in CIN than in squamous carcinoma cells, in which overexpressi on may correlate with the degree of anaplasia. (C) 1999 Academic Press.