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Clinical implications of HER‐2/neu overexpression and proteolytic activity imbalance in breast cancer
Author(s) -
Swellam Menha,
Arab Lobna R. Ezz El,
Bushnak Hussein A.
Publication year - 2007
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540701395074
Subject(s) - breast cancer , medicine , lymph node , oncology , univariate analysis , hormone receptor , cancer , proteolytic enzymes , receptor , multivariate analysis , pathology , cancer research , biology , enzyme , biochemistry
The aggressive biological behavior of invasive and metastatic cancer is considered to be the most insidious and life‐threatening aspect for breast cancer patients. It is mostly the result of changes in many molecular characteristics of tumor cells, including alterations in gene expression and the balance of proteolytic activity. The objective of this study was to determine the level of MMP‐2, its natural inhibitor TIMP‐2, their ratio and HER‐2/neu as diagnostic and prognostic factors. Markers were analyzed in 240 tissue samples categorized into 96 benign breast disease and 144 breast cancer patients. Enzyme linked immunosorbent assay procedure was used to evaluate the level of MMP‐2 and TIMP‐2 in the cell lysate, HER‐2/neu in the membrane fraction, and steroid hormone receptors (ER and PgR) in the cytosol fraction. Breast cancer patients were followed‐up for three years. Receiver operating characteristic curves were used to determine the cutoff points for the investigated factors. Positive values for all investigated factors were significantly increased in breast cancer patients compared to benign ones. Mean levels for all investigated factors were significantly correlated with lymph node and hormone receptor status, while MMP‐2 and TIMP‐2 were correlated with tumor grade (P < 0.05). In Univariate analysis, positive MMP‐2, MMP‐2/TIMP‐2, HER‐2/neu overexpression, higher tumor grade, late clinical stages and positive lymph nodes status were significantly associated with relapse. By multivariate analysis, all aforementioned factors apart from tumor grade were independent variables. Thus, the investigated markers are constructive for biologic aggressiveness of breast cancer and MMP‐2/TIMP‐2 ratio might be a new significant marker in early diagnosis and estimate prognosis in breast cancer.iubmb Life, 59: 1‐8, 2007