Matrix metalloproteinase 2 immunoreactive protein appears early in cervical epithelial dedifferentiation.

OBJECTIVE Expression of the immunoreactive protein of matrix metalloproteinase 2 (MMP-2) was studied in cervical tumors representing various stages of 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 dedifferentiation 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 expression 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 cytoplasm of the carcinoma cells. No correlation was found between overexpression of MMP-2 protein and degree of dysplasia, nor was there any association between MMP-2 and human papillomavirus (HPV). High scores for MMP-2 were observed 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 clinical course or prognosis was found. CONCLUSIONS MMP-2 expression is an early event during dedifferentiation and malignant transformation in cervical neoplasias. The pattern of staining is different in CIN than in squamous carcinoma cells, in which overexpression may correlate with the degree of anaplasia.