MICROINVASIVE CERVICAL-CARCINOMA AND CERVICAL INTRAEPITHELIAL NEOPLASIA - BIOLOGIC SIGNIFICANCE AND CLINICAL IMPLICATIONS OF 72-KDA METALLOPROTEINASE IMMUNOSTAINING

Objective: The immunohistochemical expression of 72-kDa metalloprotein ase was evaluated in cervical intraepithelial neoplasia (CIN) and micr oinvasive carcinoma, with the aim to define a relationship between 72- kDa metalloproteinase expression and neoplastic invasiveness, useful t o identify subsets of intraepithelial lesions with higher risk of prog ression. Materials and methods: Cervical bioptic samples were obtained consecutively from 54 women who attended our Colposcopic Service from January 1993 to July 1993 because of abnormal pap smear, suspicious f or cervical dysplasia and/or human papillomavirus infection. After wri tten consent, 29 women with CIN were included in the study. All women with CIN 3 lesion underwent conization; in 21 women with mild or moder ate cervical dysplasia, we did not perform any medical or physical tre atment but followed them longitudinally at close interval. After 12 mo nths, the clinical evolution was classified as spontaneous remission, persistence, or progression depending on the absence or presence of le sion and/or HPV infection in colposcopy, histology, and polymerase cha in reaction findings. In the study we also included surgical specimens from 10 women with microinvasive squamous carcinoma who underwent pri mary radical surgery. Seventy-two kilodalton metalloproteinase positiv ity was immunohistochemically stained on serial sections by using the avidin-biotin complex technique (Vector Laboratories, Burlin-game, CA) and expressed as percentage of cells per 10(3) counted neoplastic cel ls. Results: Cytoplasmatic positive 72-bDa metalloproteinase immunosta ining was significantly higher in microinvasive cervical carcinomas th an in CIN lesion (Student's t test; P < 0.001). Considering only cervi cal intraepithelial neoplasias, a significant increase in 72-kDa metal loproteinase immunostaining was observed with CIN degree increasing (o ne-way analysis of variance; P = 0.002). No correlation was found betw een 72-kDa metalloproteinase immunostaining and HPV infection and lesi on size defined by quadrants of the cervix involved with colposcopical ly evident dysplasia. By analyzing 72-kDa metalloproteinase positivity , regressive dysplasia showed low values of 72-kDa metalloproteinase i mmunostaining (median 1.2%, range 0.5-1.8%), while persistent (median 2.6%, range 1.9-3.6%) and progressive lesions (median 4.6%, range 2.3- 6.9%) presented a significantly higher positivity (one-way analysis of variance; P < 0.001). Discussion: In conclusion, the 72-kDa metallopr oteinase expression is related to invasive potential with a significan t increase in staining positivity in microinvasive carcinomas; 72-kDa metalloproteinase is detectable in cervical dysplasia, and it is relat ed to the severity of cellular atypia. A clinical implication of 72-kD a metalloproteinase immunostaining seems to be indicated, by analyzing the differences in 72-kDa metalloproteinase positivity rates between regressive and persistent or progressive disease. (C) 1996 Academic Pr ess, Inc.