PURPOSE: To assess the effect of chromosome 17 copy number on HER-2/neu status determination in breast cancers. EXPERIMENTAL DESIGN: HER-2/neu gene copy and chromosome 17 centromere numbers were evaluated on 893 breast carcinomas using double color fluorescence in situ hybridization (FISH). The net and chromosome 17 corrected (ratio) HER-2/neu copy numbers were compared and related to immunohistochemistry done according to the Food and Drug Administration (FDA)-approved scoring system (0, 1+, 2+, and 3+) as a first screening step in 584 cases. RESULTS: When a ratio > or = 2 was considered as criterion for FISH positivity, 49.3% (440 of 893) of cases showed amplification versus 56.2% (502 of 893) by using a net HER-2/neu gene copy number >4 as a alternative criterion; 14.8% (67 of 453) of cases having a ratio <2 had a net HER-2/neu gene copy number >4 and 1.1% (5 of 440) with a ratio > or = 2 had a net HER-2/neu gene copy number <4. Among discordant cases, 88.8% (64 of 72) were polysomic (>2.25 chromosomes 17/cell) and among polysomic cases, 12.8% (40 of 312) of the low polysomic (2.26-3.75 chromosomes 17/cell) and 36.9% (24 of 65) of the highly polysomic (>3.75 chromosomes 17/cell) cases showed discordance. In cases with a ratio <2, polysomy 17 incidences were 85.7% (6 of 7) in IHC 3+, 42.4% (79 of 186) in IHC 2+, 33.3% (15 of 45) in IHC 1+, and 29.1% (16 of 55) in IHC 0. CONCLUSION: A net increase in HER-2/neu gene copy number consecutive to polysomy 17 in the absence of specific gene amplification might lead to a strong protein overexpression in a small subset of breast carcinomas. HER-2/neu status determination by FISH is dependent on the criterion considered for positivity in clinical practice.
PURPOSE: To assess the effect of chromosome 17 copy number on HER-2/neu status determination in breast cancers. EXPERIMENTAL DESIGN: HER-2/neu gene copy and chromosome 17 centromere numbers were evaluated on 893 breast carcinomas using double color fluorescence in situ hybridization (FISH). The net and chromosome 17 corrected (ratio) HER-2/neu copy numbers were compared and related to immunohistochemistry done according to the Food and Drug Administration (FDA)-approved scoring system (0, 1+, 2+, and 3+) as a first screening step in 584 cases. RESULTS: When a ratio > or = 2 was considered as criterion for FISH positivity, 49.3% (440 of 893) of cases showed amplification versus 56.2% (502 of 893) by using a net HER-2/neu gene copy number >4 as a alternative criterion; 14.8% (67 of 453) of cases having a ratio <2 had a net HER-2/neu gene copy number >4 and 1.1% (5 of 440) with a ratio > or = 2 had a net HER-2/neu gene copy number <4. Among discordant cases, 88.8% (64 of 72) were polysomic (>2.25 chromosomes 17/cell) and among polysomic cases, 12.8% (40 of 312) of the low polysomic (2.26-3.75 chromosomes 17/cell) and 36.9% (24 of 65) of the highly polysomic (>3.75 chromosomes 17/cell) cases showed discordance. In cases with a ratio <2, polysomy 17 incidences were 85.7% (6 of 7) in IHC 3+, 42.4% (79 of 186) in IHC 2+, 33.3% (15 of 45) in IHC 1+, and 29.1% (16 of 55) in IHC 0. CONCLUSION: A net increase in HER-2/neu gene copy number consecutive to polysomy 17 in the absence of specific gene amplification might lead to a strong protein overexpression in a small subset of breast carcinomas. HER-2/neu status determination by FISH is dependent on the criterion considered for positivity in clinical practice.
Authors: Anna Zaczek; Aleksandra Markiewicz; Anna Supernat; Natalia Bednarz-Knoll; Burkhardt Brandt; Barbara Seroczyńska; Jarosław Skokowski; Jolanta Szade; Piotr Czapiewski; Wojciech Biernat; Marzena Wełnicka-Jaśkiewicz; Jacek Jassem Journal: Pathol Oncol Res Date: 2012-03-18 Impact factor: 3.201
Authors: Songdong Meng; Debu Tripathy; Sanjay Shete; Raheela Ashfaq; Hossein Saboorian; Barbara Haley; Eugene Frenkel; David Euhus; Marilyn Leitch; Cynthia Osborne; Edward Clifford; Steve Perkins; Peter Beitsch; Amanullah Khan; Larry Morrison; Dorothee Herlyn; Leon W M M Terstappen; Nancy Lane; Jianqiang Wang; Jonathan Uhr Journal: Proc Natl Acad Sci U S A Date: 2006-11-01 Impact factor: 11.205
Authors: Joan Albanell; Xavier Andreu; María José Calasanz; Angel Concha; José María Corominas; Tomás García-Caballero; José Antonio López; Fernando López-Ríos; Santiago Ramón y Cajal; Francisco J Vera-Sempere; Ramón Colomer; Miguel Martín; Emilio Alba; Antonio González-Martín; Antonio Llombart; Ana Lluch; José Palacios Journal: Clin Transl Oncol Date: 2009-06 Impact factor: 3.405
Authors: Fabíola E Rosa; Sara M Silveira; Cássia G T Silveira; Nádia A Bérgamo; Francisco A Moraes Neto; Maria A C Domingues; Fernando A Soares; José R F Caldeira; Silvia R Rogatto Journal: BMC Cancer Date: 2009-03-23 Impact factor: 4.430