title: MMP-2 protein in invasive breast cancer and the impact of MMP-2/TIMP-2 phenotype on overall survival.
abstract: Crucial event in the metastasis of cancer cells is the secretion of matrix metalloproteinases (MMPs), which are responsible for the degradation of extracellular matrix (ECM). Among them, matrix metalloproteinase-2 (MMP-2) is a gelatinase, which degrades basement membrane type-IV collagen. Immunohistochemistry was performed to detect MMP-2 protein in 135 infiltrative breast carcinomas. MMP-2 was studied along with clinicopathological parameters (tumor size, histological type, nuclear and histological grade, stage, lymph node status, ER, and PR), patients' survival and tissue inhibitor metalloproteinase-2 (TIMP-2), Ki-67, and p53 proteins. MMP-2 immunoreactivity was detected in the cytoplasm in cancer cells in 102 (75.6%) and in both tumor and tumor stromal cells in 37 (27.4%) of 135 cases respectively. MMP-2 reactivity in cancer cells displayed a statistically significant association with tumor size > 2 cm (p = 0.022). In tumor stromal cells a strong parallel association was observed between the expression of MMP-2 and TIMP-2 (p = 0.015), while an inverse correlation was found between MMP-2 and both Ki-67 and p53 (p = 0.033 and p = 0.034 respectively). In the subgroup with negative lymph nodes MMP-2 was also inversely associated with p53 in cancer cells (p = 0.045). Finally a statistically significant association was revealed using Kaplan-Meier and Cox's proportional hazard regression model between the MMP-2/TIMP-2 phenotype and patients' better survival (p = 0.021). Our results point out the strong relation between MMP-2 and TIMP-2 and the effect of the MMP-2/TIMP-2 phenotype in the patients' overall survival. The inverse correlation between MMP-2 and both Ki-67 and p53 can be explained by the potential inhibition of MMP-2 by TIMP-2. These results suggest the necessity of further investigation.
authors.affiliation: Department of Pathology, Medical School, The National and Kapodistrian University of Athens, Athens, Greece. lnakopou@cc.uoa.gr
authors.forename: Lydia
authors.initials: L
authors.lastname: Nakopoulou
authors.forename: Ioanna
authors.initials: I
authors.lastname: Tsirmpa
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Alexandrou
authors.forename: Androniki
authors.initials: A
authors.lastname: Louvrou
authors.forename: Constantine
authors.initials: C
authors.lastname: Ampela
authors.forename: Sophia
authors.initials: S
authors.lastname: Markaki
authors.forename: Panayiotis S
authors.initials: PS
authors.lastname: Davaris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010641:Phenotype; D016019:Survival Analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2