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Prognostic Value of ERM Gene Expression in Human Primary Breast Cancers

¹ Unité Mixte de Recherche 8117-Centre National de la Recherché Scientifique, Régulation Transcriptionnelle au cours de la Tumorigenèse Mammaire, Institut de Biologie de Lille, Institut Pasteur de Lille, Lille Cédex, France; ² Laboratoire de Biologie du Développement, UPRES 1033, Université des Sciences et Techniques de Lille-Flandres-Artois, Villeneuve d’Ascq Cédex, France; ³ Laboratoire d’Oncologie Moléculaire Humaine and ⁴ Laboratoire de Cytologie et Anatomie Pathologiques, Centre Oscar Lambret, 59020 Lille Cédex, France; and ⁵ Laboratoire de Virologie Moléculaire-Faculté de Médecine, Université Libre de Brussels, Brussels, Belgium

We measured the expression of ERM gene, a nuclear transcription factor belonging to the ets family, in a series of 364 unselected primary breast cancers from patients who underwent locoregional surgery in the Centre Oscar Lambret between May 1989 and December 1991. The expression of ERM was quantified with a real-time one-step reverse transcription-PCR assay based on the 5'-nuclease activity of the TaqDNA polymerase and with an Abi Prism 7700 Sequence Detector System (Applied Biosystems, Courtaboeuf, France). ERM was positively correlated (Spearman test) to epidermal growth factor receptor (EGFR; P < 0.001, r = 0.296) and to histoprognostic grading (P = 0.044, r = 0.112), whereas it was negatively correlated to estradiol receptors (P = 0.019, r = -0.124), HER3 (c-erbB-3; P = 0.01, r = –0.135), and HER4 (c-erbB-4; P = 0.003, r = –0.154). Using the ² test, a positive relationship was found between the expression of ERM and EGFR (² = 7.795, P = 0.007). In overall survival studies, Cox univariate analyses demonstrated a prognostic value of ERM (P = 0.006; risk ratio, 2.95) besides the classical prognostic factors histoprognostic grading, node involvement, tumor size, estradiol receptors, progesterone receptors, EGFR, HER3, and HER4. In multivariate analyses, ERM preserved its prognostic value (P = 0.004; risk ratio, 3.779) together with histoprognostic grading, tumor size, estradiol receptors, and progesterone receptors. In relapse-free survival studies, univariate analyses demonstrated that histoprognostic grading, node involvement, tumor size, and HER4 were prognostic factors. These parameters, except histoprognostic grading, retained their prognostic value in multivariate analyses. This study demonstrates for the first time that ERM gene expression is an independent adverse prognostic factor for overall survival in breast cancer patients.

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