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.