Matrix metalloproteinase-1 and -3 in breast cancer: correlation with progesterone receptors and other clinicopathologic features.
Although matrix metalloproteinases (MMPs) are implicated in breast cancer progression, the contribution of MMP-1 and MMP-3 to this process, has not been thoroughly investigated. Matrix metalloproteinases (MMPs) are important at several points during multistage neoplastic progression. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1, MMM-3 proteins, and MMP-3 mRNA, respectively, in 77 infiltrative breast carcinomas. MMP-1, MMP-3 protein, and MMP-3 mRNA detection were analyzed in parallel with clinicopathologic features (menopausal status, histological type, nuclear and histological grade, stage) and the immunohistochemical reactivity of estrogen (ER), progesterone (PR) receptors, and c-erbB-2 oncoprotein in breast carcinomas. Statistical analysis was performed using the multiple linear regression test. Immunoreactivity for MMP-1 and MMP-3 was observed in 59 of 77 (77%) and 22 of 77 (28.5%) breast carcinomas and was evaluated separately in cancer cells and in stromal fibroblasts. MMP-3 mRNA was detected in 72 of 77 (93.5%) carcinomas exclusively in stromal cells within the tumors or in the marginal portion of tumors. MMP-1 protein immunoreactivity in stromal fibroblasts but not in cancer cells showed a statistically significant correlation with tumor stage (P=.04). MMP-1 reactivity either in stromal or in cancer cells showed a statistically significant inverse correlation with PR expression (P=.04 and P=.04, respectively). MMP-3 protein immunoreactivity in cancer or stromal cells and MMP-3 mRNA expression was not associated with the clinicopathologic features studied. MMP-3 mRNA was detected more often in ductal carcinomas. These results indicate that MMP-1 may contribute to breast cancer invasiveness. Furthermore, they suggest differential functions for MMP-1 and MMP-3 in breast cancer progression.
Nakopoulou
L
L
Department of Pathology, Medical School, University of Athens, Greece.
Giannopoulou
I
I
Gakiopoulou
H
H
Liapis
H
H
Tzonou
A
A
Davaris
P S
PS
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D017364:Collagenases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016014:Linear Models; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism*
D012333:RNA, Messenger; D011980:Receptors, Progesterone; D017364:Collagenases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1