Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinase-3 and -4 in normal ovary and ovarian carcinoma.

The objective of this study was to determine the spatial expression of matrix metalloproteinases (MMPs) and their physiologic inhibitors, the tissue inhibitor of MMP (TIMP)-3 and TIMP-4, in ovarian carcinoma compared to normal ovaries. Immunohistochemistry was carried out in this study. Tissue sections prepared from normal ovarian tissues from throughout the menstrual cycle (N = 20) and ovarian carcinomas (N = 45) characterized as stage I (N = 5), stage III/IV (N = 40) were immunostained using polyclonal antibodies to the latent and the active form of MMP-26, TIMP-3, and a monoclonal antibody to TIMP-4. Immunoreactive MMP-26, TIMP-3, and TIMP-4 were detected in all the ovarian cell types in normal and tumor tissues. In normal ovarian tissues, theca externa and luteal cells immunostained with high intensity for MMP-26 and TIMPs while theca/granulosa cell staining intensity increased as lutenization progressed. There was low immunostaining of the ovarian stromal and surface epithelial cells for MMP-26, with moderate staining for TIMPs. In the carcinoma specimens, cancer cells and vascular endothelial cells displayed the highest staining intensity compared to adjacent nontumor areas. The immunostaining intensity of MMP-26 and TIMP-3 increased with stage of tumor with the invading tumor cells displaying the strongest immunostaining. MMP-26, TIMP-3, and TIMP-4 are expressed in normal ovarian as well as ovarian tumors with elevated expression in the invasive tumor cells suggesting a potential role for MMP-26 in normal ovary and ovarian cancer biologic function.