PMID- 28712009 OWN - NLM STAT- MEDLINE DCOM- 20180601 LR - 20180601 IS - 1573-7217 (Electronic) IS - 0167-6806 (Linking) VI - 166 IP - 1 DP - 2017 Nov TI - Analysis of molecular subtypes for the increased HER2 equivocal cases caused by application of the updated 2013 ASCO/CAP HER2 testing guidelines in breast cancer. PG - 77-84 LID - 10.1007/s10549-017-4397-z [doi] AB - PURPOSE: Accurate testing of the status of human epidermal growth factor receptor type 2 (HER2) is a prerequisite for HER2-directed therapy. The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) published joint guideline recommendations for HER2 testing in breast cancer in 2007 and it was updated in 2013. We compared the HER2 gene amplification status based on these two guidelines and analyzed the molecular characteristics of the equivocal cases. PATIENTS AND METHODS: A total of 1894 patient samples were analyzed for both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 FISH amplification was examined and re-assessed using 2013 guidelines. RESULTS: According to the 2013 ASCO/CAP recommendations, 763 (40.3%) cases were classified as HER2 positive compared with 729 (38.5%) cases defined by 2007 guidelines. There was a significant increase of 6.1% in the proportion of HER2 FISH equivocal cases that were interpreted using ASCO/CAP 2013 (7.3%) compared with 2007 (1.2%) guidelines (P < 0.001). Of 138 FISH equivocal cases defined by 2013 guidelines, 125 cases were IHC2+ and 13 cases were IHC1+. These 125 cases included 4 double equivocal cases which were defined as equivocal by both 2007 and 2013 guidelines and 121 cases whose status was changed from negative defined by 2007 guidelines to equivocal defined by 2013 guidelines. Compared with luminal A type and luminal B type respectively, these 121 equivocal cases demonstrated no significant difference with luminal B type in T stage and N stage (P = 0.192, P = 0.421). When we divided the luminal B type into two parts that included HER2 negative cases and HER2 positive cases, the equivocal cases also showed no significant difference with these two subtypes in T stage and N stage. CONCLUSIONS: Our study suggested that implementation of the revised ASCO/CAP 2013 guidelines resulted in an increase of 1.7% in overall HER2 positivity rate and of 6.1% in equivocal cases. Pathological analysis revealed that these equivocal cases exhibit similar biological behavior with luminal B type tumors. Clinical utility data on targeted therapy in equivocal patients should be further investigated. FAU - Guo, Lei AU - Guo L AD - Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. FAU - Yuan, Pei AU - Yuan P AD - Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. FAU - Zhang, Jing AU - Zhang J AD - Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. FAU - Ling, Yun AU - Ling Y AD - Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. FAU - Li, Wenbin AU - Li W AD - Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. FAU - Zhao, Bohui AU - Zhao B AD - Department of Breast Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. FAU - Ying, Jianming AU - Ying J AD - Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. jmying@hotmail.com. FAU - Xuan, Lixue AU - Xuan L AD - Department of Breast Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. xuanlx@hotmail.com. LA - eng PT - Journal Article DEP - 20170715 PL - Netherlands TA - Breast Cancer Res Treat JT - Breast cancer research and treatment JID - 8111104 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - *Biomarkers, Tumor MH - Breast Neoplasms/*diagnosis/*genetics MH - Female MH - Gene Amplification MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - *Molecular Diagnostic Techniques MH - Neoplasm Grading MH - Neoplasm Staging MH - Practice Guidelines as Topic MH - Receptor, ErbB-2/*genetics/metabolism OTO - NOTNLM OT - Breast cancer OT - Equivocal cases OT - Fluorescence in situ hybridization OT - HER2 OT - Immunohistochemistry EDAT- 2017/07/18 06:00 MHDA- 2018/06/02 06:00 CRDT- 2017/07/17 06:00 PHST- 2017/04/12 00:00 [received] PHST- 2017/07/11 00:00 [accepted] PHST- 2017/07/18 06:00 [pubmed] PHST- 2018/06/02 06:00 [medline] PHST- 2017/07/17 06:00 [entrez] AID - 10.1007/s10549-017-4397-z [pii] AID - 10.1007/s10549-017-4397-z [doi] PST - ppublish SO - Breast Cancer Res Treat. 2017 Nov;166(1):77-84. doi: 10.1007/s10549-017-4397-z. Epub 2017 Jul 15.