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

• Published in: Clinical cancer research 2006-08, Vol.12 (15), p.4533-4544
• Main Authors: GINESTIER, Christophe, CERVERA, Nathalie, CHAFFANET, Max, BIMBAUM, Daniel, BERTUCCI, Francois, FINETTI, Pascal, ESTEYRIES, Séverine, ESTERNI, Benjamin, ADDLAIDE, José, XERRI, Luc, VIENS, Patrice, JACQUEMIER, Jocelyne, CHARAFE-JAUFFRET, Emmanuelle
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - surgery; Cancer; Cellular Biology; chromosome 20; Chromosomes, Human, Pair 20 - genetics; Cluster Analysis; DNA microarrays; Female; Gene Amplification; Gene Expression Profiling; Gynecology. Andrology. Obstetrics; Humans; In Situ Hybridization, Fluorescence; Kaplan-Meier Estimate; Life Sciences; Mammary gland diseases; Medical sciences; Middle Aged; Oligonucleotide Array Sequence Analysis - methods; Pharmacology. Drug treatments; Prognosis; Reverse Transcriptase Polymerase Chain Reaction - methods; Survival Rate; Tissue Array Analysis - methods; Treatment Outcome; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-2339

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.