RECURRENCE PATTERNS IN LOCALLY ADVANCED CERVICAL-CARCINOMA - ROLE OF NODAL STATUS AND 72-KDA METALLOPROTEINASE INDEX

Objective: The aim of the study was to analyze the relationship betwee n lymph nodal involvement and regional and/or distant recurrences in l ocally advanced squamous cervical carcinomas, and also evaluate tumor 72-kDa metalloproteinase, as a biologic parameter useful for understan ding the mechanisms of disease relapse and prognosis. In particular, 7 2-kDa metalloproteinase is an enzyme that specifically cleaves type IV collagen and seems to play a critical role in tumor invasion and meta static dissemination. Methods: The medical records of 62 patients with FIGO (International Federation of Gynecology and Obstetrics) stage Ib and IIa squamous cervical carcinoma who underwent primary radical sur gery with systematic pelvic and paraaortic lymphadenectomy and then we re routinely followed were recruited from our series of 76 consecutive cases and reviewed. Fifty-four patients with complete clinicopatholog ic information were considered eligible for the study. All recurrences were defined as histologically and/or cytologically documented diseas e, following a minimum 3-month disease-free interval. Sites of recurre nces were classified as distant, or regional to the pelvis. Immunostai ning with 72-kDa metalloproteinase was performed on serial sections of tumors using avidin-biotin complex technique. Affinity-purified rabbi t anti-72-kDa metalloproteinase antibody was used. Positive staining w as expressed as a percentage of positive cells per 10(3) counted neopl astic cells (72-kDa metalloproteinase index). Results: After a median followup of 38 months (range 9-71 months), 11 patients recurred with a 20% overall incidence. Seven patients (64%) recurred regionally, with side-wall infiltration in 2 cases, and 4 patients (36%) recurred dist antly. By Cox hazard multivariate analysis, lymph nodal status was sig nificantly related to disease-free survival (P = 0.01); in particular, all the patients with side-wall or distant recurrences had lymph noda l involvement. A significant relationship was also observed between tu mor 72-kDa metalloproteinase immunostaining and disease-free survival (P = 0.02). The 72-kDa metalloproteinase index was significantly highe r in patients who recurred than in patients with disease-free follow-u p (P < 0.001); in particular, the highest values were detected in pati ents who recurred distantly. A relationship between 72-kDa metalloprot einase staining and nodal status was observed (P < 0.001). Conclusions : In conclusion, nodal status and the 72-kDa metalloproteinase index w ere two independent prognostic parameters, significantly related to re currence risk and pattern of recurrence in locally advanced cervical c arcinoma. Although they are independent prognostic parameters, a relat ionship between nodal involvement and 72-kDa metalloproteinase was obs erved. A model of tumor recurrence in which intrinsic tumor factors ex ert their negative influence directly or by contributing to the develo pment of nodal metastases seems possible. (C) 1996 Academic Press, Inc .