Our study attempts to determine the prognostic value of the quantitative measurement of the oncoprotein p185Her-2/neu in a group of patients with breast cancer and positive node involvement. In a series of 217 patients with breast cancer and positive nodes in whom the oncoprotein p185 was quantitatively determined by ELISA, we analyzed the clinicopathological variables including age, menopausal status, tumor size, number of affected nodes, type and histology grade and the molecular variables such as the oestrogen and progesterone receptors (ER and PR, respectively), pS2 and Cathepsin D (CD). Using 260 fmol/mg protein as a cut-off point, 18% of the tumors presented as overexpressing p185. The p185 showed no relationship with any of the clinico-pathological variables studied except that its concentration was elevated in ductal and lobular histology types and in the moderate and poorly differentiated histology grades. With a median follow-up of 50 months (range 1-90), the univariate analysis of disease-free survival (DFS) and overall survival (OS) showed that the histology grade, tumor size, the number of infiltrated nodes, the p185 and the ER were the variables associated with the clinical course of the disease in the patients. In the multivariate analysis, however, only the tumor size, number of affected ganglia, the p185 and the ER remained associated with the clinical progression of the disease. The patients with p185 overexpression had a risk, not only of relapse but also death from the disease, of more than twice that of the patients who had normal p185 concentrations. When the p185 was divided into 3 categories based on ؎1 ؋ SD above or below the mean, the patients with high and low p185 showed, in the univariate analysis, a similar relationship with DFS but not with OS. In the multivariate analysis, both with the DFS as with the OS, only a high p185 concentration retained its association with the clinical course of the disease in the patients. Our results suggest that by quantitatively determining (using ELISA) the p185 oncoprotein, groups of cancer patients of high risk could be better identified for more effective clinical management. © 2002 Wiley-Liss, Inc. Key words: breast cancer; p185 oncoprotein; ELISAThe HER-2/neu proto-oncogene encodes a 185-kDa trans-membrane glycoprotein (p185) that is a growth factor receptor with tyrosine-kinase activity. The gene amplification or p185 oncoprotein is overexpressed in ϭ30% of cases of human breast cancer 1,2 and has been shown to be associated with a poorer prognosis. [3][4][5][6] The HER-2 gene status has also been studied in conjunction with other prognostic biological markers such as positive node involvement, histological grade, size of tumor, oestrogen (ER) and progesterone (PR) steroid receptor, Cathepsin D (Cat D) and pS2. 7-10The overexpression of p185 has been measured, usually, using immunohistochemical methods and Western blot analysis. 4,[11][12][13][14][15] Recently, a quantitative assay 16 -18 has been employed for the determination of p185. We ha...

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The total cellular p185 HER-2/neu protein (p185) content was measured by ELISA in 346 invasive primary breast cancers, and the results were compared with those of estrogen (ER) and progesterone (PR) receptors, pS2 and Cathepsin D (Cat D) content. At a cut-off level of 260 fmol/mg protein, 53 of the 346 tumors (15%) were p185-positive. A significant positive correlation was observed between p185 levels and those of Cat D, and a weaker, though significant, positive correlation with ER, and pS2 levels, but not with those of PR. However, when only the 293 p185-negative tumors were considered, the correlation between p185 and ER improved substantially, and statistical significance was reached for PR. p185-positive tumors exhibited lower ER and PR content and higher Cat D content than p185-negative tumors. The pS2 content, in contrast, did not undergo significant variation. Tumors considered to be p185-positive were significantly more frequently positive for Cat D at the cut-off of 45 pmol/mg protein, and were more frequently negative for ER and/or PR, but only significant at the cut-off of 15 fmol/mg or higher for both steroid receptors. Finally, p185 status was not associated with menopausal status, tumor size, axillary-lymph-node invasiveness or distant metastases. These results suggest that 260 fmol/mg protein as the cut-off for p185 allows the identification of a tumoral sub-population with a more aggresive phenotype. Int.

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