Reappraisal of HER2 Amplification in High-Grade Urothelial Carcinoma Based on 2018 ASCO/CAP Clinical Practice Guidelines. Issue 6 (14th June 2021)

• Record Type: Journal Article
• Authors: Mohanty, Sambit K; Mishra, Sourav K; Tiwari, Ankit; Sharma, Shivani; Bhardwaj, Mohit; Pattnaik, Niharika; Jaiswal, Sunil; Baisakh, Manas R; Das, Subodh; Pradhan, Manas R; Swain, Tapas R; Satpathy, Kaliprasad; Williamson, Sean R; Parwani, Anil V
• Is Part Of: American journal of clinical pathology. Volume 156:Issue 6(2021)
• Page Start: 1130
• Page End: 1141
• Publication Date: 2021-06-14
• Subjects: HER2 -- FISH -- High-grade bladder cancer -- ASCO/CAP practice guidelines; Diagnosis, Laboratory -- Periodicals; Pathology -- Periodicals; 616.07
• DOI: 10.1093/ajcp/aqab083
• Languages: English
• ISSNs: 0002-9173

Abstract

Abstract: Objectives: To examine and compare human epidermal growth factor receptor 2 ( HER2 ) amplification status in high-grade urothelial carcinoma (HGUCa), using both 2013 and 2018 HER2 reporting guidelines for breast carcinoma from the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP). Methods: HER2 status by fluorescence in situ hybridization (FISH) assay in 78 cases of HGUCa was compared using 2013 and 2018 HER2 reporting guidelines. Results: HER2 amplification was observed in 22 (28.2%) of 78 tumors, of which 17 were in group 1, 1 in group 2, and 2 each in groups 3 and 4 (FISH assay, 2018). The remaining 14 HER2- amplified tumors (FISH assay, 2013) became negative, falling into group 2 (FISH assay, 2018) and were either negative or equivocal on immunohistochemistry (IHC, 2018). All FISH-negative tumors (n = 37) using 2013 criteria remained negative (group 5, 2018). FISH-equivocal tumors (2013) were further categorized into HER2 amplified (n = 1) and HER2 negative (n = 4) (2018). Overall, 20 (25.6%) tumors had discordant HER2 FISH results (2018 vs 2013). Conclusions: Implementing 2018 guidelines, HER2 amplification decreased from 36 to 22 cases. The group with a HER2 /CEP17 ratio of 2 or more and average HER2 copy number less than 4 (group 2) were predominantly negative by IHC, suggesting a biologically distinct group of HGUCa that is different from HER2 -amplified tumors, which may not respond to HER2-targeted therapy.