PMID- 12111403 OWN - NLM STAT- MEDLINE DCOM- 20021204 LR - 20041117 IS - 0918-4287 (Print) IS - 0918-4287 (Linking) VI - 35 IP - 1 DP - 2002 Mar TI - Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinase, collagens, and Ki67 antigen in pleural malignant mesothelioma: an immunohistochemical and electron microscopic study. PG - 16-23 AB - Because matrix metalloproteinases (MMPs) degrade extracellular matrix, including basement membrane, and because tissue inhibitors of MMP (TIMPs) suppress MMP activities, MMPs and TIMPs are considered to play important roles in invasion and metastasis in many malignancies. We examined immunohistochemically the expression of MMPs (MMP-1, -2, -3, -7, and -9), TIMPs (TIMP-1 and -2), and collagens (types I, III, and IV) in 16 patients with pleural malignant mesothelioma (PMM; 8 with the epithelial, 4 with the sarcomatous, and 4 with the biphasic type). Electron microscopy revealed that the tumor cells in all types possessed the characteristics of malignant mesotheliomas, including numerous microvilli and moderate amounts of intermediate filaments. Basement lamina was present only focally. The proliferative Ki67 index was at a high level, compared with values reported in various other malignancies. Positive staining for MMP-1 was observed in most tumor cells in all 16 patients (100%). MMP-2 was expressed in most tumor cells in 2 patients (13%). In contrast, MMP-3, -7, and -9 were not detected in any PMM. TIMP-1 and TIMP-2 were expressed in 3 patients (19%) and 2 patients (13%), respectively. The stromal cells were simultaneously positive for MMPs or TIMPs in the patients whose tumor parenchymal cells were positive for each enzyme. These results indicate that the expression of MMP-1 and MMP-2 may be related to PMM invasion and spread. In particular, as MMP-1 was overexpressed in contrast to the lower expression of TIMP-1, MMP-1 is strongly suggested to play an important role in PMM invasion by degrading the tumor stroma. In spite of general agreement that epithelial-type PMM has a better prognosis than other types, there was no significant difference in the Ki67 index among the histological types of PMM. FAU - Hirano, Hiroshi AU - Hirano H AD - Department of Pathology, Osaka Medical College, Osaka, Japan. patho@toneyama.hosp.go.jp FAU - Tsuji, Motomu AU - Tsuji M FAU - Kizaki, Tomohiko AU - Kizaki T FAU - Sashikata, Terumasa AU - Sashikata T FAU - Yoshi, Yasuyoshi AU - Yoshi Y FAU - Okada, Yoshikatsu AU - Okada Y FAU - Mori, Hiroshi AU - Mori H LA - eng PT - Journal Article PL - Japan TA - Med Electron Microsc JT - Medical electron microscopy : official journal of the Clinical Electron Microscopy Society of Japan JID - 9430789 RN - 0 (Ki-67 Antigen) RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - 9007-34-5 (Collagen) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Aged MH - Collagen/*metabolism MH - Female MH - Humans MH - Immunohistochemistry MH - Ki-67 Antigen/*metabolism MH - Male MH - Matrix Metalloproteinases/*metabolism MH - Mesothelioma/*metabolism/ultrastructure MH - Microscopy, Electron MH - Middle Aged MH - Mitotic Index MH - Pleural Neoplasms/*metabolism/ultrastructure MH - Tissue Inhibitor of Metalloproteinases/*metabolism EDAT- 2002/07/12 10:00 MHDA- 2002/12/05 04:00 CRDT- 2002/07/12 10:00 PHST- 2002/07/12 10:00 [pubmed] PHST- 2002/12/05 04:00 [medline] PHST- 2002/07/12 10:00 [entrez] AID - 10.1007/s007950200002 [doi] PST - ppublish SO - Med Electron Microsc. 2002 Mar;35(1):16-23. doi: 10.1007/s007950200002.