The 72-kDa metalloproteinase immunostaining in cervical carcinoma: Relationship with lymph nodal involvement

Objective: In the present study we detected 72-kDa metalloproteinase expression in our series of early stage cervical carcinomas and analyzed the relationship between 72-kDa metalloproteinase staining and risk of nodal involvement with the goal of identifying a parameter useful in predicting the metastatic potential of lesions. Materials and Methods: The medical records of 34 patients with PICO stage I squamous cell cervical carcinoma who had undergone primary radical surgery with systematic pelvic and paraaortic lymphadenectomy (Fiver's type III) at the Institute of Gynecologic and Obstetrics, Ancona University, between January 1988 and January 1993 were recruited from our series of 57 consecutive cases and reviewed. Any characteristic that could be relevant for prognosis was recorded in all of the cases: histologic grade of differentiation, tumor size, lymphatic spread, and adjuvant radiotherapy. Immunohistochemical staining was performed on serial sections of tumors using the avidin-biotin complex technique (Vector Laboratories, Burlingame, CA). The affinity-purified rabbit anti-72-kDa metalloproteinase antibody was used. Positive staining was expressed as a percentage of positive cells per 103 counted neoplastic cells (the 72-kDa metalloproteinase index). Results: The tissue 72-kDa metalloproteinase immunoreactivity was diffusely expressed in all cervical carcinomas (ranging from 8.6 to 51.9%, with a median of 17.8%) and showed a significant relationship with respect to lymphatic spread. In the presence of lymph nodal involvement, the 72-kDa metalloproteinase index was significantly higher than in the absence of nodal metastasis (32.9 +/- 12.2% versus 18.1 +/- 9.0%, means +/- standard deviations with P = 0.001); a significant relationship was also observed between the 72-kDa metalloproteinase index and the number of positive nodes (r = 0.8, with P = 0.01). No significant relationship was defined with respect to the other prognostic parameters. The Cox proportional hazard analysis showed a significant relationship between the 72-kDa metalloproteinase index and disease-free survival (P < 0.0001) that was independent of tumor size, nodal involvement, and lymphvascular space invasion. Conclusions: Although the small numbers do not allow any definitive conclusion, a significant relationship between the 72-kDa metalloproteinase index and the risk of lymphatic spread is defined in early stage cervical carcinoma. The 72-kDa metalloproteinase immunostaining seems to have a prognostic value, suggesting the possibility of an association between neoplastic aggressiveness and 72-kDa metalloproteinase expression. (C) 1996 Academic Press, Inc.