Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication

Abstract

Collecting duct carcinoma (CDC) is rare and aggressive histology of kidney cancers. Although different therapeutic approaches have been tested, the 2-year survival remains very poor. Since CDC exhibits overlapping features with urothelial carcinoma, the analysis of shared molecular alterations could provide new insights into the understanding of this rare disease and also therapeutic options. We collected 26 CDC cases, and we assessed HER2 protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in-situ hybridization (FISH) according to 2018 ASCO/CAP HER2-testing recommendations. Six out of twenty-six (23%) tumors showed HER2 positive staining. In particular, 3+ score was present in 2/6 cases (33%), 2+ in 3/6 cases (50%) and 1+ in 1/6 cases (17%). The 6 HER2+ tumors were also analyzed by FISH to assess gene copy number. One out of six CDC with IHC 3+ was also HER2 amplified, showing an average HER2 copy number ≥4.0 (10.85) and a HER2/CEP17 ratio ≥ (5.63), while the 5/6 cases were HER2 negative. Based on the 2018 ASCO/CAP guidelines overall, 2/26 CDC cases (8%) were HER2+. The present study provides evidence for testing, in future studies, HER2 to assess its clinical value as a novel target for the treatment of this highly malignant cancer.

Assessment of the expression pattern of HER2 and its correlation with HER2-targeting antibody-drug conjugate therapy in urothelial cancer

“…Human epidermal growth factor receptor 2 (HER2) abnormalities, including protein overexpression, gene amplification and mutation, play an important role in the carcinogenesis and development of many cancers, including urothelial cancer. Gene amplification or protein overexpression of HER2 occurs in 15%−20% of breast cancer cases, 1 10%−30% of gastric cancer cases, 20%−30% of ovarian cancer cases 2 and 8% of renal collecting duct carcinoma cases 3 ; it is associated with tumor progression and poor prognosis. In bladder carcinoma, HER2 overexpression is correlated with more aggressive behavior and poor outcome, with an overexpression [immunohistochemistry (IHC) 3+] rate of 12.4% (59/475).…”