PMID- 15743507 OWN - NLM STAT- MEDLINE DCOM- 20060131 LR - 20220408 IS - 1465-542X (Electronic) IS - 1465-5411 (Print) IS - 1465-5411 (Linking) VI - 7 IP - 2 DP - 2005 TI - 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. PG - R267-73 AB - 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 chi2 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. FAU - Salido, Marta AU - Salido M AD - Laboratori de Citogenetica i Biologia Molecular, Servei de Patologia, Hospital del Mar, IMAS, Barcelona, Spain. MSALIDO@IMAS.IMIM.ES FAU - Tusquets, Ignasi AU - Tusquets I FAU - Corominas, Josep M AU - Corominas JM FAU - Suarez, Marta AU - Suarez M FAU - Espinet, Blanca AU - Espinet B FAU - Corzo, Cristina AU - Corzo C FAU - Bellet, Meritxell AU - Bellet M FAU - Fabregat, Xavier AU - Fabregat X FAU - Serrano, Sergi AU - Serrano S FAU - Sole, Francesc AU - Sole F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050126 PL - England TA - Breast Cancer Res JT - Breast cancer research : BCR JID - 100927353 RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Breast Neoplasms/*genetics MH - *Chromosome Aberrations MH - *Chromosomes, Human, Pair 18 MH - Female MH - Gene Amplification MH - Gene Dosage MH - Gene Expression Profiling MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Prospective Studies MH - Proto-Oncogene Mas MH - Receptor, ErbB-2/*biosynthesis/genetics MH - Up-Regulation PMC - PMC1064140 EDAT- 2005/03/04 09:00 MHDA- 2006/02/01 09:00 PMCR- 2005/01/26 CRDT- 2005/03/04 09:00 PHST- 2004/08/19 00:00 [received] PHST- 2004/11/08 00:00 [revised] PHST- 2005/01/05 00:00 [accepted] PHST- 2005/03/04 09:00 [pubmed] PHST- 2006/02/01 09:00 [medline] PHST- 2005/03/04 09:00 [entrez] PHST- 2005/01/26 00:00 [pmc-release] AID - bcr996 [pii] AID - 10.1186/bcr996 [doi] PST - ppublish SO - Breast Cancer Res. 2005;7(2):R267-73. doi: 10.1186/bcr996. Epub 2005 Jan 26.