72-KILODALTON TYPE-IV COLLAGENASE, TYPE-IV COLLAGEN, AND KI-67 ANTIGEN IN SEROUS TUMORS OF THE OVARY - A CLINICOPATHOLOGICAL, IMMUNOHISTOCHEMICAL, AND SEROLOGICAL STUDY

The immunohistochemical expression of 72-kDa type IV collagenase [matr ix-metalloproteinase (MMP)-2], basement membrane component type IV col lagen and proliferation-related antigen Ki 67 were investigated in 43 benign, borderline, and malignant serous tumors of the ovary. The resu lts were compared with the histotypes of ovarian serous tumors and wit h their clinical behavior. Serum evaluation of MMP-2 was performed in 14 patients with cystadenocarcinoma and the data compared with that of a control group. The basement membrane (BM) was continuous in benign cystadenomas and in some borderline tumors, whereas it was discontinuo us or absent in other borderline tumors, in borderline tumors with mic roinvasion, and in cystadenocarcinomas. The percentage of MMP-2- and K i 67-expressing cells increased from cystadenomas to borderline tumors , being the highest in malignant tumors; a frequent basal disposition of the MMP-2 cytoplasmic granules also was observed in cystadenocarcin omas. Statistical analysis demonstrated that MMP-2 expression was inve rsely related to BM integrity. Serum MMP-2 values did not differ from that of the control group. Cox regression analysis showed that tumor s tage and grade were significant prognostic factors, whereas MMP-2 and Ki 67 immunohistochemical expression added no further significant info rmation to the prognosis. The investigators conclude that the correlat ion between increasing MMP-2 expression and BM alteration gives suppor t to the hypothesis of a direct role of the metalloproteinase in the p rocess of destructive stromal invasion. MMP-2, type IV collagen, and K i 67 immunodetection varied according to the histologic classification of ovarian serous tumors. However, neither these factors nor the seru m evaluation of MMP-2 appear useful as prognostic predictors in this s eries.