Genetic Alterations in HER2-Positive and Equivocal Breast Cancer by Immunohistochemistry

Yi-Fang Tsai,1– 3 Chih-Yi Hsu,3,4 Yun-Ning Chiu,1,5 Chi-Cheng Huang,1,6 Shih-Hsiang Chou,1 Yen-Shu Lin,1– 3 Ta-Chung Chao,1,3,7 Chun-Yu Liu,1,3,8,* Jen-Hwey Chiu,1,2,9,* Ling-Ming Tseng1– 3 1Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112201, Taiwan; 2Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112201, Taiwan; 3Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112201, Taiwan; 4Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, 112201, Taiwan; 5Division of General Surgery, Department of Surgery, Shaung Ho Hospital, Taipei Medical University, Taipei City, 23561, Taiwan; 6Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, 100233, Taiwan; 7Division of Cancer Prevention, Department of Oncology, Taipei Veterans General Hospital, Taipei, 112201, Taiwan; 8Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, 112201, Taiwan; 9Division of General Surgery, Department of Surgery, Cheng-Hsin General Hospital, Taipei, 112401, Taiwan*These authors contributed equally to this workCorrespondence: Jen-Hwey Chiu, Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei City, 112201, Taiwan, Tel +886-2-55681176, Fax +886-2-55681185, Email [email protected]: We aimed to identify genetic alterations in groups with different HER2 immunohistochemical (IHC) scores.Patients and Methods: A total of 120 patients with HER2-positive breast cancers, including 89 cases with IHC 3+ tumors and 31 cases with IHC 2+ and positive for in situ hybridization (ISH) were enrolled. Molecular profiles were determined using Thermo Fisher TMO comprehensive assay on surgically removed tissues. All called variants were compared between IHC3+ and IHC2+/ISH+ groups by Fisher exact test.Results: There was a significantly higher sample frequency 94.4% (84/89) of ERBB2 amplification in IHC3+ group than that in IHC2+/ISH+ group 45.2% (14/31). By contrast, there was a significantly lower sample frequency of MYC_AMP_CNA 10.1% (9/89) and CCND3_AMP_CNA 0% (0/89) in IHC3+ group than those in IHC2+/ISH+ group with sample frequency 25.8% (8/31), and 9.7% (3/31), respectively.Conclusion: We conclude that HER2 IHC3+ tumors have higher frequency of ERBB2_ AMP_CNA and lower frequency of CCND3_ AMP_CNA and MYC_AMP_CNA than IHC2+/ISH+ tumors. These results provide therapeutic strategies in treatment of HER2-positive breast cancer.Keywords: genetic alteration, CNA, erbb2, breast cancer, immunohistochemistry