title: HER2 Status in Gastroesophageal Adenocarcinomas: Correlation Between Immunohistochemistry and Fluorescence In Situ Hybridization Methodologies.
abstract: Semiquantitative immunohistochemistry (IHC) is commonly used in combination with fluorescence in situ hybridization (FISH) to detect HER2 amplification in gastroesophageal adenocarcinomas. Most laboratories apply these tests in a sequential algorithm, using IHC as a frontline test and reserving FISH for IHC-equivocal cases. To gain a better understanding of the concordance of IHC and FISH results at our institution, we identified all gastroesophageal adenocarcinomas at our institution tested for HER2 (n=125). Matched IHC and FISH were available for 116 cases (94%). Cases consisted of adenocarcinoma of the distal esophagus (22%), gastroesophageal junction (24%), stomach (43%), and metastatic sites (12%). A total of 88 cases (70%) were biopsies, whereas 37 cases (30%) were resections. Overall, 15 cases (13%) were HER2 positive (IHC 3+ and/or FISH amplified). A total of 60 cases (52%) were IHC score 0; none of these were HER2 amplified by FISH. A total of 30 cases (26%) were IHC 1+; 5 (17%) of these cases were HER2 amplified by FISH. A total of 20 cases (17%) were IHC 2+; 4 (20%) of these cases were HER2 amplified by FISH. A total of 6 cases were IHC score 3+; all of these were HER2 amplified by FISH. Although there was a high overall concordance between IHC and FISH results (96%), a subset (17%) of IHC-negative cases (score 1+) were HER2 amplified as evaluated by FISH, representing 33% of all HER2 amplified cases. This suggests that the common practice of limited FISH testing to IHC 2+ cases will miss a significant number of HER2 amplified cases.
authors.affiliation: Departments of Pathology.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Robertson
authors.affiliation: Departments of Pathology.|Oncology, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Ashley
authors.initials: A
authors.lastname: Cimino-Mathews
authors.affiliation: Departments of Pathology.
authors.forename: Toby C
authors.initials: TC
authors.lastname: Cornish
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003951:Diagnostic Errors; D004943:Esophagogastric Junction / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards*; D017404:In Situ Hybridization, Fluorescence / Q000592:standards*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases