title: Genetic heterogeneity of HER2 in breast cancer: impact on HER2 testing and its clinicopathologic significance.
abstract: In 2009, ASCO/CAP expanded its human epidermal growth factor receptor type 2 (HER2) testing guideline to define HER2 genetic heterogeneity (GH). However, the clinical significance of GH is unclear. We investigated the impact of HER2 GH on HER2 testing and studied its clinicopathologic significance. Paraffin-embedded tumor tissues of surgical resections of 617 non-consecutive breast carcinoma patients were studied by routine HER2 fluorescence in situ hybridization (FISH). HER2 GH was evaluated, and the results were correlated with HER2 protein expression by immunohistochemistry and HER2 gene amplification by FISH, and with various clinicopathologic parameters. HER2 GH was observed in 15.2 % (94/617) of the patients. It was associated with low-to-middle level of HER2 expression, and with none-to-low level of HER2 gene amplification. Among the 17 patients with equivocal HER2 FISH results, 35.3 % (6/17) of tumors displayed GH. In contrast with HER2-positive tumors without GH, tumors with HER2 GH demonstrated significant association with lower histologic grade, smaller tumor size, and proclivity to hormone receptor expression. HER2 GH is a substantial cause of equivocal HER2 testing results of breast cancer by FISH. Tumors with HER2 GH showed that biologic features resemble more of HER2-negative tumors than HER2-positive tumors without GH. The findings indicate a need of the guidelines to clarify whether tumors with HER2 GH truly benefit from HER2-targeted therapy of breast cancer.
authors.affiliation: Department of Breast Cancer Pathology and Research Laboratory, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute & Hospital, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin 300060, China.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Fan
authors.forename: Rong-Gang
authors.initials: RG
authors.lastname: Lang
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: Mei-Jing
authors.initials: MJ
authors.lastname: Ren
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Yin
authors.forename: Li
authors.initials: L
authors.lastname: Fu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D018740:Genetic Heterogeneity; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases