Localization of MT1-MMP, TIMP-1, TIMP-2, and TIMP-3 messenger RNA in normal. hyperplastic, and neoplastic endometrium - Enhanced expression by endometrial adenocarcinomas is associated with low differentiation

We studied membrane-type matrix metalloproteinnse-1 (MT1-MMP), tissue inhib itor of metalloproteinase-1 (TIMP-1), TIMP-2 and TIMP-3 messenger RNA (mRNA ) using in situ hybridization to elucidate their temporal and spatial expre ssion patterns in normal, hyperplastic, and neoplastic endometrium. All mRN As studied were expressed weakly, in proliferating endometrium but were ind uced strongly in late secretory endometrium except MT1-MMP Endometrial hype rplasia samples did not show increased MT1-MMP or TIMP mRNA expression, ind icating that the overall expression patterns in hyperplasia are comparable to those in proliferating endometrium under estrogen effect and that synthe sis of extracellular matrix proteins, rather than degradation, predominates in this condition. Exceptionally, stromal cells in areas of desquamation w ere seen to express focally, intense MT1-MMP mRNA in hyperplasia samples. A ll mRNAs investigated It ere expressed increasingly in endometrial adenocar cinomas, especially in less differentiated carcinomas. Furthermore, gelatin zymography revealed higher functional degradative activities in carcinoma tissues than in normal endometrium. Our results indicate that MT1-MMP expre ssion, together with that of TIMPs, is involved most notably in normal endo metrium under progesterone effect and, without being connected to cyclic ho rmonal levels, has an important role in the invasive growth of endometrial adenocarcinomas.