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BMC Cancer

, 14:959

Cell and molecular biology


BackgroundMetalloproteinases MMPs and their tissue inhibitors of metalloproteinases TIMPs are involved in several key pathways of tumor growth, invasion and metastasis, but little is known about their expression according to different molecular subtypes of breast cancer. The aims of this study were to assess the prevalence and clinical significance of MMP and TIMP expression in invasive breast cancer and to determine its association with immunohistochemical-based molecular classification.

MethodsTissue microarray sections were immunostained for estrogen receptor-α ER-α, progesterone receptor PR, human epidermal growth factor receptor 2 HER2, cytokeratin CK 5-6, epidermal growth factor receptor EGFR and with specific antibodies against MMP-1, 2, 7, 9, 11, 13, and 14 and TIMP-1, 2, and 3. Based on the immunostaining data from five of the markers used ER-α, PR, HER2, EGFR and CK5-6, three major subtypes 123 luminal A, 31 basal-like, and 17 HER2-overexpressing were selected.

ResultsStatistically significant differences in the expression of MMPs and TIMPs among the three subtypes were found in tumoral MMP7 P = 0.005, tumoral MMP-9 P = 0.000, tumoral MMP-13 P = 0.016 and stromal MMP-13 P = 0.016. The incidence of tumoral MMP-9 expression in the HER2-overexpressing subtype was significantly higher than in the luminal A subtype P = 0.021. Tumoral MMP-9 and stromal MMP-13 expression were significantly higher in the HER2-overexpressing subtype than in the basal-like subtype P = 0.000 and P = 0.016, respectively. Tumoral MMP-7 expression was significantly higher in the basal-like subtype compared to luminal A P = 0.007 and HER2-overexpressing subtype P = 0.004. Tumoral MMP-13 showed a higher expression in the basal-like subtype than in the HER2-overexpressing subtype P = 0.010. In multivariate analysis, stage and stromal MMP-1 expression were significantly related to overall survival. Stage was of independent prognostic significance for disease-free survival.

ConclusionWe found some variations in MMP and TIMP expression among the immunohistochemical-based molecular subtypes of breast carcinomas, suggesting differences in their tumor pathophysiology. Additional studies are needed to determine the mechanisms underlying the differences of MMP and TIMP expression in the molecular subtypes for the development of specific therapeutic targets for breast cancer subtypes.

KeywordsBreast cancer Molecular subtype Immunohistochemistry Matrix metalloproteinase Tissue inhibitor of metalloproteinase AbbreviationsMMPmetalloproteinase

TIMPtissue inhibitors of metalloproteinase TIMP

ER-αestrogen receptor-α

PRprogesterone receptor

HER2human epidermal growth factor receptor 2


EGFRepidermal growth factor receptor.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-14-959 contains supplementary material, which is available to authorized users.

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Autor: Ga-Eon Kim - Ji Shin Lee - Yoo-Duk Choi - Kyung-Hwa Lee - Jae Hyuk Lee - Jong Hee Nam - Chan Choi - Sung Sun Kim - Min


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