Abstract

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 the mechanisms controlling cell growth and proliferation. The aim of this retrospective study was to identify predictors of aggressive biological behavior and metastatic potential in breast carcinoma among a number of intrinsic biomarkers of tumor cells such as steroid receptors and oncogene and tumor suppressor gene products. Routine formalin-fixed, paraffin-embedded tumor samples were used and sections were stained immunohistochemically with the DAKO Strept ABC method to determine the expression of estrogen receptors (ER), progesterone receptors (PgR), HER-2/neu, bcl-2, Ki-67, p53 and nm23 in 192 consecutive breast carcinoma patients. The results of the quantitative immunohistochemical assays were correlated with clinical and histological data such as patient age, overall survival, tumor size, axillary lymph node status, hystological type, tumor grade, Nottingham prognostic index (NPI) and therapeutic regimens. Univariate analysis revealed that survival was significantly longer for patients with small tumors (P = 0.007), lower tumor grade (P = 0.021), negative axillary lymph nodes (P = 0.002), presence of nm23 protein (P = 0.002), and for patients treated with adjuvant hormonal therapy (P = 0.010). In multivariate analysis the independent factors positively affecting survival were absence of axillary lymph node metastases (P = 0.002), nm23 expression (P = 0.009) and hormonal therapy (P = 0.050). Among patients with positive axillary nodes there was a significantly higher survival rate in patients with nm23 expression compared with nm23-negative patients (P < 0.001). Identification of a subset of node-positive breast cancer patients with a more favorable prognosis according to nm23 expression might be clinically useful.

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