PMID- 31640438 OWN - NLM STAT- MEDLINE DCOM- 20201130 LR - 20201130 IS - 1940-2465 (Electronic) IS - 1066-8969 (Linking) VI - 28 IP - 3 DP - 2020 May TI - The Utility of ERBB4 and RB1 Immunohistochemistry in Distinguishing Chromophobe Renal Cell Carcinoma From Renal Oncocytoma. PG - 259-264 LID - 10.1177/1066896919883016 [doi] AB - Objectives. Differentiating renal oncocytoma (RO) from chromophobe renal cell carcinoma (ChRCC) can occasionally be challenging. We evaluated the expression of RB1 and ERBB4 in RO and ChRCC, and compared the immunohistochemistry (IHC) results to RB1 and ERBB4 gene abnormalities detected by fluorescence in situ hybridization (FISH). Materials and Methods. Fifty-three kidney resections (ChRCC, n=28; RO, n=25) were stained for RB1 and ERBB4 IHC and FISH was performed to evaluate gene copy number analysis. Results. A loss of RB1 staining was identified in 64% (18/28) of ChRCCs, which was not found in any ROs (0/25; P <.001). FISH analysis revealed 36% (10/28) of ChRCCs contained a RB1 hemizygous deletion with a concordance of 56% (10/18) between the IHC and FISH findings. No RB1 gene copy number variations were detected in any of the ROs (0/25; P <.001) and retained expression of RB1 by IHC. ERBB4 showed cytoplasmic/membranous staining in all ROs and ChRCCs. However, 75% (21/28) of ChRCCs also contained nuclear positivity for ERBB4, which was uncommonly seen in ROs (3/25, 12%; P < .001). A hemizygous ERBB4 gene deletion was detected in 46% of ChRCCs (13/28), but none of the ROs (0/25; 0%). Loss of labeling by RB1 or nuclear staining for ERBB4 IHC identified 25 of 28 (89%) of ChRCCs. Conclusion. In summary, the loss of RB1 expression is a highly specific diagnostic biomarker in distinguishing ChRCC from RO. Nuclear ERBB4 expression also appears to be a sensitive diagnostic biomarker for ChRCC, albeit the mechanism is unknown. FAU - Sun, Tong AU - Sun T AD - University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA, USA. FAU - Hutchinson, Lloyd AU - Hutchinson L AD - University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA, USA. FAU - Zhou, Amy G AU - Zhou AG AD - University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA, USA. AD - Johns Hopkins University, Baltimore, MD, USA. FAU - Liu, Qingqing AU - Liu Q AD - University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA, USA. AD - Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Cosar, Ediz F AU - Cosar EF AD - University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA, USA. FAU - St Cyr, Maryann AU - St Cyr M AD - University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA, USA. FAU - Ninteau, Nicole AU - Ninteau N AD - University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA, USA. FAU - Dresser, Karen AU - Dresser K AD - University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA, USA. FAU - Cheng, Liang AU - Cheng L AD - Indiana University, Indianapolis, IN, USA. FAU - Jiang, Zhong AU - Jiang Z AD - University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA, USA. FAU - Cornejo, Kristine M AU - Cornejo KM AUID- ORCID: 0000-0002-9490-8583 AD - University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA, USA. AD - Massachusetts General Hospital, Boston, MA, USA. LA - eng PT - Journal Article DEP - 20191022 PL - United States TA - Int J Surg Pathol JT - International journal of surgical pathology JID - 9314927 RN - 0 (Biomarkers, Tumor) RN - 0 (RB1 protein, human) RN - 0 (Retinoblastoma Binding Proteins) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.7.10.1 (ERBB4 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-4) RN - Oncocytoma, renal SB - IM MH - Adenoma, Oxyphilic/*diagnosis MH - Biomarkers, Tumor/*analysis MH - Carcinoma, Renal Cell/*diagnosis MH - Diagnosis, Differential MH - Humans MH - Immunohistochemistry MH - Kidney Neoplasms/*diagnosis MH - Receptor, ErbB-4/analysis/*biosynthesis MH - Retinoblastoma Binding Proteins/analysis/*biosynthesis MH - Ubiquitin-Protein Ligases/analysis/*biosynthesis OTO - NOTNLM OT - ERBB4 OT - RB1 OT - chromophobe renal cell carcinoma OT - fluorescence in situ hybridization OT - immunohistochemistry OT - renal oncocytoma EDAT- 2019/10/24 06:00 MHDA- 2020/12/01 06:00 CRDT- 2019/10/24 06:00 PHST- 2019/10/24 06:00 [pubmed] PHST- 2020/12/01 06:00 [medline] PHST- 2019/10/24 06:00 [entrez] AID - 10.1177/1066896919883016 [doi] PST - ppublish SO - Int J Surg Pathol. 2020 May;28(3):259-264. doi: 10.1177/1066896919883016. Epub 2019 Oct 22.