Evaluation of HER-2/neu oncogene status in breast tumors on tissue microarrays.
The amplification and/or overexpression of the HER-2/neu oncogene and its encoded receptor protein are increasingly used for prognostication and prediction of therapeutic response to Herceptin in breast cancer. However, large-scale examination of archival tumor blocks by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) is prohibitively laborious and technically challenging. The tissue microarray (TMA) technique enables hundreds of tumors to be studied simultaneously in a single experiment. To evaluate the HER-2/neu status of a selection of the breast tumors in our tumor bank, we constructed a TMA from 97 breast tumors, with a single 0.6-mm core per specimen. HER-2/neu gene amplification by FISH was found in 20 of the 87 interpretable cases (23%): in 14 of 14 IHC 3+ cases (100%), 5 of 8 IHC 2+ cases (62.5%) and 1 of 65 IHC 0/1+ cases (1.5%). Three of the 67 cases with no evidence of HER-2/neu gene amplification by FISH were moderately positive (2+) by IHC. A close relationship was observed between these 2 assays as applied to the TMA (95.4% concordance: 95% CI, -2.2% to 6.8%; P <0.0001), and both HER-2/neu gene amplification and protein overexpression were strongly associated with tumor grade, estrogen receptor status, and progesterone receptor status. Gene amplification was found in most of the tumors with high-level overexpression (IHC 3+) and not in the unequivocal IHC-negative cases. Complementary analysis by IHC and FISH are, however, recommended for tumors graded as 2+ by IHC, the group with the most result discrepancy. Hum Pathol 34:362-368.
Molecular Diagnosis Centre, Department of Laboratory Medicine, National University Hospital and Department of Pathology, National University of Singapore, Singapore.
Daohai
D
Zhang
Manuel
M
Salto-Tellez
Elaine
E
Do
Thomas Choudary
TC
Putti
Evelyn S C
ES
Koay
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D016591:Histocytological Preparation Techniques / Q000379:methods*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011933:Reagent Kits, Diagnostic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
D011933:Reagent Kits, Diagnostic; D018719:Erb-b2 Receptor Tyrosine Kinases