title: A potential pitfall in evaluating HER2 immunohistochemistry for gastric signet ring cell carcinomas.
abstract: Signet ring cell carcinoma (SRC) more commonly presents as metastatic disease and renders patients to be considered for chemotherapy. While treatment options are limited overall, trastuzumab has been shown to be effective for HER2 positive SRC cases. The current algorithm for HER2 evaluation heavily relies on positive membrane-specific staining by immunohistochemistry (IHC), but several anecdotal reports have suggested that SRCs may be susceptible to misinterpretation due to non-specific staining in the marginated cytoplasm with/without nucleus. Results of two FDA-approved IHC methods of HER2 evaluation, Pathway and HercepTest, along with silver in situ hybridisation were interpreted retrospectively and compared in 155 primary SRC cases. IHC results were discrepant between the two assays in SRC even at the strongest IHC scores. Discordance indeed occurred due to dark, non-specific staining obscured by the unique SRC morphology. True HER2 positive SRC was identified in three cases (3/155, 1.9%). In this study, we demonstrate the importance of recognising potential discrepancy in interpreting HER2 status depending on the assay used. Understanding this possible pitfall may prevent unnecessary trastuzumab in SRC patients.
authors.affiliation: Department of Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of medicine, Bucheon, Gyeonggi-do, Republic of Korea.
authors.forename: Chang Gok
authors.initials: CG
authors.lastname: Woo
authors.affiliation: Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Won Jin
authors.initials: WJ
authors.lastname: Ho
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: youngspark@amc.seoul.kr.
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sook Ryun
authors.initials: SR
authors.lastname: Park
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Ryu
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Hwoon-Yong
authors.initials: HY
authors.lastname: Jung
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D018279:Carcinoma, Signet Ring Cell / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000068878:Trastuzumab / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Gastric cancer; HER2; immunohistochemistry; signet ring cell carcinoma; trastuzumab