Human epidermal growth factor receptor 2 (

objectivesTo evaluate human epidermal growth factor receptor 2 (HER2) protein overexpression by immunohistochemistry (IHC) and gene amplification by fluorescent PATIENTS AND

methodsThe study included 93 bladder cancers; 25 MIBC and 68 NMIBC (37 low- and 31 high-grade). All HER2 positive (3+) and equivocal (2+) cases were subjected to FISH using a HER2/CEN 17 dual-colour probe kit. IHC and FISH were scored as per the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2013 Guidelines for breast cancers. Based on the number of signals/nuclei, amplification was categorised as low (≥6-10) and high-level (≥10).

resultsHER2 2-3+ expression was seen in 29% of NMIBCs (10.8% low- and 51.6% high-grade). HER2 3+ expression was seen in high-grade NMIBC (nine of 31; 29%) and MIBC (nine of 25; 36%). In all, 87% of high-grade NMIBCs were lamina invasive (pT1). Gene amplification was found in 45% (eight of 18) of 3+ tumours. None of the HER2 2+ tumours showed gene amplification. IHC and FISH results were in closest agreement when ≥50% of tumour cells showed 3+ expressions. High-level amplification correlated with increased gene expression on reverse transcriptase-polymerase chain reaction. On multivariate analysis, lower  stage, grade, and HER2 expression significantly correlated with progression-free survival. HER2 3+ expression in NMIBC correlated significantly with time to recurrence and progression.

conclusionOur present results show that HER2 FISH should not be performed for HER2 2 + and low-grade NMIBC. This contrasts with breast cancers where it is recommended for equivocal 2+ tumours. About 50% of HER2 3+ MIBC and high-grade NMIBC show ABBREVIATIONS: ASCO/CAP: American Society of Clinical Oncology/College of American Pathologists; DAB: 3,3'-diaminobenzidine; FISH: fluorescent