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Prognosis and Gene Expression Profiling of 20q13-Amplified Breast Cancers

Authors' Affiliations: ¹ Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, UMR599 Inserm; ² Département d'Oncologie Médicale et Investigation Clinique; ³ Laboratoire de BioPathologie, Institut Paoli-Calmettes; and ⁴ Université de la Méditerranée, UFR de Médecine, Marseilles, France

Requests for reprints: Daniel Birnbaum, UMR599 Inserm, 27 Bd. Leï Roure, 13009 Marseilles, France. Phone: 33-4-91-75-84-07; Fax: 33-4-91-26-03-64; E-mail: birnbaum{at}marseille.inserm.fr.

Purpose: Amplification of chromosomal region 20q13 occurs in breast cancer but remains poorly characterized.

Experimental Design: To establish the frequency of 20q13 amplification and select the amplified cases to be studied, we used fluorescence in situ hybridization of bacterial artificial chromosome probes for three 20q13 loci (MYBL2, STK6, ZNF217) on sections of tissue microarrays containing 466 primary carcinoma samples. We used Affymetryx whole-genome DNA microarrays to establish the gene expression profiles of 20q13-amplified tumors and quantitative reverse transcription-PCR to validate the results.

Results: We found 36 (8%) 20q13-amplified samples. They were distributed in two types: type 1 tumors showed ZNF217 amplification only, whereas type 2 tumors showed amplification at two or three loci. Examination of the histoclinical features of the amplified tumors showed two strikingly opposite data. First, type 1 tumors were more frequently lymph node–negative tumors but were paradoxically associated with a poor prognosis. Second, type 2 tumors were more frequently lymph node–positive tumors but were paradoxically associated with a good prognosis. Type 1 and type 2 showed different gene expression profiles. No 20q13 gene could be associated with type 1 amplification, whereas several 20q13 genes were overexpressed in type 2 tumors.

Conclusions: Our results suggest that amplified tumors of types 1 and 2 are two distinct entities resulting from two different mechanisms and associated to different prognosis.

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