Research article

Polysomy of chromosome 17 in breast cancer tumors showing an overexpression of ERBB2: a study of 175 cases using fluorescence in situ hybridization and immunohistochemistry

Marta Salido^1,2,3 , Ignasi Tusquets^3,4,5 , Josep M Corominas^3,5,6 , Marta Suarez^3,4 , Blanca Espinet^1,2 , Cristina Corzo^1,3,4,5 , Meritxell Bellet^3,4 , Xavier Fabregat^3,4 , Sergi Serrano^5,6 and Francesc Solé^1,2,3

¹Laboratori de Citogenètica i Biologia Molecular, Servei de Patologia, Hospital del Mar, IMAS, Barcelona, Spain

²Escola de Citologia Hematològica S Woessner-IMAS, Hospital del Mar, IMAS-IMIM, Barcelona, Spain

³Unitat de Recerca translacional en tumors sòlids-IMAS, Barcelona, Spain

⁴Servei d'Oncologia Mèdica, Hospital del Mar, IMAS, Barcelona, Spain

⁵Universitat Autònoma de Barcelona, Barcelona, Spain

⁶Servei de Patologia, Hospital del Mar, IMAS, Barcelona, Spain

author email corresponding author email

Breast Cancer Res 2005, 7:R267-R273doi:10.1186/bcr996

Published:	26 January 2005

Abstract

Introduction

One of the most common genetic aberrations associated with breast cancer is the amplification and overexpression of the ERBB2 proto-oncogene located at chromosome 17, bands q12-21. The amplification/overexpression occurs in 25 to 30% of all breast cancers. In breast cancer, aneusomy of chromosome 17, either monosomy or polysomy, is frequently observed by conventional cytogenetics and fluorescence in situ hybridization (FISH). The aim of this study was to discover whether or not numerical aberrations on chromosome 17 have a correlation to the amplification or overexpression of the ERBB2 gene and to analyze their clinical implications in subgroups showing 2+ or 3+ positive scores by immunohistochemistry (IHC).

Methods

We used FISH on a series of 175 formalin-fixed paraffin-embedded breast carcinomas to detect ERBB2 amplification, using a dual-probe system for the simultaneous enumeration of the ERBB2 gene and the centromeric region of chromosome 17, as well as using IHC to detect overexpression. We analyzed clinical and pathological variables in a subgroup of patients with 2+ and 3+ IHC scores (147 patients), to describe any differences in clinicopathological characteristics between polysomic and non-polysomic cases with the use of the χ² test.

Results

We found 13% of cases presenting polysomy, and three cases presented monosomy 17 (2%). According to the status of the ERBB2 gene, instances of polysomy 17 were more frequently observed in non-amplified cases than in FISH-amplified cases, suggesting that the mechanism for ERBB2 amplification is independent of polysomy 17. Polysomy 17 was detected in patients with 2+ and 3+ IHC scores. We found that nodal involvement was more frequent in polysomic than in non-polysomic cases (P = 0.046).

Conclusions

The determination of the copy number of chromosome 17 should be incorporated into the assesment of ERBB2 status. It might also be helpful to differentiate a subgroup of breast cancer patients with polysomy of chromosome 17 and overexpression of ERBB2 protein that probably have genetic and clinical differences.