Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay

We measured the expression of the type I growth factor receptor gene family [epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3 and c-erbB-4] in a series of 365 unselected primary breast cancers. The expression was q uantified with a real-time one-step reverse transcriptase-PCR (RT-PCR) assa y, based upon the 5' nuclease activity of the Tao polymerase and using an A bi Prism 7700 Sequence Detector System (Perkin-Elmer, Courtaboeuf, France). c-erbB-3 and c-erbB-4 were positively correlated to each other (Spearman t est) and negatively correlated to EGFR, EGFR and c-erbB-2 were inversely co rrelated to the presence of estradiol receptors (ER) and progesterone recep tors (PgR), and positively correlated to the histoprognostic grading (HPG), Conversely, c-erbB-3 and c-erbB-4 were positively correlated to the presen ce of ER and PgR, and inversely correlated to the grading HPG, EGFR was inv ersely related (chi (2) test) to the presence of ER and PgR, and positively associated with HPG. In contrast, both c-erbB-3 and c-erbB-4 were inversel y related to HPC, and positively associated with the presence of ER and PgR , The expression level of EGFR and c-erbB-2 was significantly higher in ER- and PgR-negative tumors compared with ER- and PgR-positive tumors (Student 's t test), and in tumors with higher grade compared with tumors with lower grade. The expression level of c-erbB-3 and c-erbB-4 was significantly hig her in ER- and PgR-positive tumors compared with ER- and PgR-negative tumor s and in tumors with lower grade compared with tumors with higher grade. In overall survival studies, Cox univariate analyses showed prognostic values of EGFR [greater than or equal to median; P = 0.026; risk ratio (RR), 1.6] , c-erbB-3 (greater than or equal to median; P = 0.0093; RR, 0.58), c-erbB- 4 (greater than or equal to median; P = 0.0024; RR, 0.52), HPG, node involv ement, tumor diameter, ER, and PgR, In Cox multivariate analyses, tumor dia meter, ER, and PgR had a prognostic value. In relapse-free survival studies , univariate analyses demonstrated prognostic values of tumor diameter, nod e involvement, and c-erbB-4 (P = 0.015; RR, 0.65), These three parameters m aintained their prognostic value in multivariate analyses (c-erbB-4, P = 0. 035; RR, 0.67), This study confirms that EGFR expression and c-erbB-2 expre ssion are markers of tumor aggressiveness in breast cancer. Conversely, we demonstrate that c-erbB-3 and c-erbB-4 elevated expressions are associated with a better prognosis.