Amplification as a Predictive and Prognostic Biomarker in Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinomas (UTUCs) occur in about 5-10% of all urothelial carcinomas and are frequently discovered in high-stage disease. We aimed to evaluate human epidermal growth factor receptor 2 (ERBB2) protein expression immunohistochemically and amplification in UTUCs by fluorescence in situ hybridization, applying a tissue microarray technique. ERBB2 overexpression and amplification were defined according to the recommendations of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) for breast cancer and gastric carcinoma (GC), revealing scores of 2+ and 3+ in 10.2% and 41.8% of UTUCs, respectively. The performance parameters showed obviously higher sensitivity of ERBB2 immunoscoring according to the ASCO/CAP criteria for GC. amplification was detected in 10.5% of UTUCs. ERBB2 overexpression was more likely to be found in high-grade tumors and was associated with tumor progression. Univariable Cox regression analysis revealed a significantly lower progression-free survival (PFS) in cases with ERBB2 immunoscores of 2+ or 3+ according to the ASCO/CAP guidelines for GC. UTUCs with amplification showed a significantly shorter PFS in the multivariable Cox regression analysis. Irrespective of their status, patients with UTUC treated with platin showed a significantly lower PFS than UTUC patients who had not received any platin-based therapy. In addition, UTUC patients with a normal gene status who had not received platin-based therapy showed significantly longer overall survival. The results suggest that ERBB2 is a biomarker for progression in UTUCs and may define a distinct subgroup of UTUCs. As previously shown, amplification is infrequent. However, the small number of patients diagnosed with -amplified UTUC might benefit from ERBB2-targeted cancer therapy. In clinical-pathological routine diagnostics, the determination of amplification is an established method in some defined entities and also successful in small samples. Still, the simultaneous use of ERBB2 immunohistochemistry and in situ hybridization would be important in order to record the low rate of amplified UTUC cases as completely as possible.