Prognostic values of ETS-1, MMP-2 and MMP-9 expression and co-expression in breast cancer patients

Abstract

The aim of this study was to analyse expression of ETS-1 protein and two gelatinases (MMP-2 and MMP-9) and their possible prognostic value in breast carcinoma patients, as well as correlation of their expression with other known prognostic factors such as tumor size, grade, vascular invasion, steroid receptor values, HER2 values and proliferative index. The expression of MMP-2, MMP-9 and ETS-1 was immunohistochemicaly analysed in 121 consecutive primary breast carcinoma patients who underwent surgery at the Clinical Hospital Centre Zagreb during 2002. Three representative areas from each tumor paraffin blocks were taken and arranged on a recipient paraffin block with predefined coordinates for simultaneous analyses of multiple tissue samples (TMA). ETS-1, MMP-2 and MMP-9 expression and co-expression were correlated with other clinico-pathological parameters and based on the available clinical follow up data survival analysis was performed.The ETS-1 protein is found to be expressed in tumor cell nuclei and cytoplasm as well as in stromal lymphocytes, fibroblasts and endothelial cells. MMP-2 and MMP-9 were found to be expressed in cytoplasm of both, tumor and stromal cells. For our analysis only tumor cell expression was used for statistical analysis. We found 56,2% ETS-1 positive tumors, 77,7% were MMP-2 positive, and MMP-9 was expressed in 90% of primary breast carcinomas. There were no significant correlations between MMP-s expression and other patohistological prognostic factors, but expression of ETS-1 was significantly correlated with higher tumor size and grade, as well as with negative steroid receptors. Co-expression of MMP-2, MMP-9 and ETS-1 was found in 40,5 % of tumors, and more commonly was found in tumors larger than 2 cm, high grade tumors, and steroid receptor negative tumors. In univariate analysis, statistically significant negative impact on overall survival (OS) had tumor size, nuclear and tumor grade, ETS-1 expression in tumor cells, co-expression of ETS-1 either with MMP-2 or MMP-9, as well as co-expression of ETS-1, MMP-2 and MMP-3. Disease free survival (DFS) was significantly shorter in patients with tumors greater than 2 cm, ETS-1 positive tumors, ETS-1 and MMP-2 or MMP-9 co-expressed tumors, and additionally in tumors with ETS-1, MMP-2 and MMP-9 co-expression. These results suggest that expression of ETS-1 as well as MMP-2, MMP-9 and ETS-1 co-expression might be used as a poor prognostic factor in breast cancer patients.

New Therapeutic Schedule for Prostatic Cancer-3 Cells with ET-1 RNAi and Endostar

“…In addition, the combined effect of these two treatments was stronger than that of single. According to previous reports, MMP-2 and MPP-9 played the important role in the invasion of cancer cells (Fiorentini et al, 2014;Puzovic et al, 2014). In this study, we found that the expression of MMP-2 and MMP-9 were both reduced obviously in the treatment groups.…”

Extracellular matrix in obesity – cancer interactions

“…Moreover, MMPs are also linked with inflammation through recruitment of a variety of stromal cells such as fibroblasts and leukocytes [77]. Expectantly, many investigators observed a connection between adverse clinical outcome in breast cancer patients and higher blood levels and/or tumor tissue expression of MMP-2 and MMP-9 [78,79]. Fascinatingly, MMP-9 has been shown to be correlated with the overexpression of poor prognosis marker HER2 [78,80].…”

The transforming growth factor beta-1 in the oncogenesis of human lung adenocarcinoma

“…Повышенная активность ETS1 наблюдалась при РМЖ, РЛ, раке яичников, обо-дочной и прямой кишки и меланоме [33][34][35][36][37]. ETS1 сверхэкспрессируется при инвазивном РМЖ и корре-лирует с его плохим прогнозом [38]. Высокая экспрес-сия ETS1 способствует миграции раковых клеток, инвазии и анкернезависимому росту, в то же время низкая экспрессия ETS1 снижала адгезию клеток HeLa [39].…”