Expression of tissue inhibitor of matrix metalloproteinases TIMP-3 protein in invasive breast carcinoma: Relation to tumor phenotype and clinical outcomeReportar como inadecuado




Expression of tissue inhibitor of matrix metalloproteinases TIMP-3 protein in invasive breast carcinoma: Relation to tumor phenotype and clinical outcome - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Breast Cancer Research

, 8:R57

First Online: 10 October 2006Received: 15 June 2006Revised: 28 July 2006Accepted: 10 October 2006

Abstract

IntroductionOur aim was to study the expression pattern of tissue inhibitor of metalloproteinases TIMP-3 protein in invasive breast carcinoma, and its clinicopathological and prognostic value as well as its relation to markers indicative of the tumor phenotype.

MethodsImmunohistochemistry was performed on paraffin-embedded tissue specimens from 173 invasive breast carcinomas to detect the proteins TIMP-3, estrogen receptor ER, progesterone receptor, p53, c-erbB-2, topoisomerase IIα and Bcl-2.

ResultsTIMP-3 protein was immunodetected in the cytoplasm of the malignant cells and the peritumoral stroma, as well as in in situ carcinoma and normal epithelium. Reduced expression of TIMP-3 protein within cancer cells was correlated with carcinomas of high nuclear and histological grade p = 0.032 and p = 0.015, respectively, and low ER expression p = 0.053. Moreover, TIMP-3 immunopositivity was inversely correlated with the expression of p53 and topoIIα proteins p = 0.002 and p = 0.008, respectively, whereas it was positively associated with Bcl-2 expression p = 0.020. Reduced expression of TIMP-3 protein within cancer cells was found to have an unfavorable impact on disease-free survival p = 0.052 in the entirety of the patient population, as well as in both subgroups of lymph-node-positive and mutant-p53-negative patients p = 0.007 and p = 0.037, respectively. Stromal localization of TIMP-3 protein was found to have no clinicopathological or prognostic value.

ConclusionThis is the first immunohistochemical study to show that TIMP-3 protein within cancer cells is associated with tumor phenotype. Reduced expression of TIMP-3 protein within cancer cells was found to correlate with an aggressive tumor phenotype, negatively affecting the disease-free survival of both subgroups of lymph node-positive and mutant-p53-negative patients.

AbbreviationsERestrogen receptor

MMPmatrix metalloproteinase

PRprogesterone receptor

TIMPtissue inhibitor of metalloproteinases.

Electronic supplementary materialThe online version of this article doi:10.1186-bcr1607 contains supplementary material, which is available to authorized users.

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Autor: Eleni Mylona - Christina Magkou - Ioanna Giannopoulou - George Agrogiannis - Sofia Markaki - Antonios Keramopoulos - Lydia 

Fuente: https://link.springer.com/







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