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

• Published in: Clinical cancer research 2000-11, Vol.6 (11), p.4217-4225
• Main Authors: PAWLOWSKI, Valérie, REVILLION, Francoise, HEBBAR, Mohamed, HORNEZ, Louis, PEYRAT, Jean-Philippe
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Female; Genes, erbB-2; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Prognosis; Receptor, Epidermal Growth Factor - genetics; Receptor, ErbB-3 - genetics; Receptor, ErbB-4; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Tumors
• ISSN: 1078-0432; 1557-3265

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 quantified with a real-time one-step reverse transcriptase-PCR (RT-PCR) assay, based upon the 5′ nuclease activity of the Taq polymerase and using an Abi Prism 7700 Sequence Detector System (Perkin-Elmer, Courtaboeuf, France). c-erbB-3 and c-erbB-4 were positively correlated to each other (Spearman test) and negatively correlated to EGFR. EGFR and c-erbB-2 were inversely correlated to the presence of estradiol receptors (ER) and progesterone receptors (PgR), and positively correlated to the histoprognostic grading (HPG). Conversely, c-erbB-3 and c-erbB-4 were positively correlated to the presence of ER and PgR, and inversely correlated to the grading HPG. EGFR was inversely related (χ 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 inversely related to HPG, 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 higher in ER- and PgR-positive tumors compared with ER- and PgR-negative tumors and in tumors with lower grade compared with tumors with higher grade. In overall survival studies, Cox univariate analyses showed prognostic values of EGFR [≥ median; P = 0.026; risk ratio (RR), 1.6], c-erbB-3 (≥ median; P = 0.0093; RR, 0.58), c-erbB-4 (≥ median; P = 0.0024; RR, 0.52), HPG, node involvement, tumor diameter, ER, and PgR. In Cox multivariate analyses, tumor diameter, ER, and PgR had a prognostic value. In relapse-free survival studies, univariate analyses demonstrated prognostic values of tumor diameter, node involvement, and c-erbB-4 ( P = 0.015; RR, 0.65). These three parameters maintained 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 expression 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.