Clinical Utility of Chromosome Genomic Array Testing for Unclassified and Advanced-Stage Renal Cell Carcinomas

Cytogenomic analysis provides a useful adjunct to traditional pathology in the categorization of renal cell carcinomas (RCCs), particularly in morphologically ambiguous cases, but it has disadvantages, including cost.

To define the clinical scenarios in which this technology has direct clinical applications.

DNA was isolated from paraffin-embedded tissue from 40 selected cases of RCC. Chromosome genomic array testing was performed using the OncoScan.

Of 23 cases of unclassified renal tumors, 19 (83%) were reclassified with incorporation of cytogenetic and histologic features, including 10 as clear cell RCC, 2 as collecting duct carcinoma, 2 as papillary RCC, and 1 as novel TFEB-amplified tumor lacking TFEB translocation. Of 5 tumors with "hybrid" oncocytic features, 3 were reclassified as an eosinophilic variant of chromophobe RCC and 1 as oncocytoma. Appropriate staging in 2 patients was determined by identifying distinct, nonshared cytogenetic profiles. Of 11 cases of metastatic clear cell RCC, 7 (63%) had cytogenetic features associated with a poor prognosis.

We identified 5 scenarios in which chromosome genomic array testing has direct clinical utility: (1) to investigate unclassified RCCs, (2) to understand tumors with "hybrid" features and "collision" tumors, (3) to determine appropriate staging in questions of bilateral tumors and/or metastases, (4) to identify chromosomal aberrations in metastatic clear cell RCCs associated with a worse prognosis, and (5) to identify new entities. This has practical value in our institution, where a molecular profile diagnostically separating morphologically difficult to classify clear cell, papillary, chromophobe, and unclassified RCC influences treatment recommendations and clinical trial eligibility.

Archives of pathology & laboratory medicine. 2018 Nov 01 [Epub ahead of print]

Nicole K Andeen, Xiaoyu Qu, Tatjana Antic, Scott S Tykodi, Min Fang, Maria S Tretiakova

From the Department of Pathology, University of Washington, Seattle (Drs Andeen and Tretiakova); the Department of Pathology, Oregon Health & Science University, Portland (Dr Andeen); Cytogenetics, Seattle Cancer Care Alliance, Seattle, Washington (Dr Qu); the Department of Pathology, University of Chicago, Chicago, Illinois (Dr Antic); and the Division of Medical Oncology, Department of Medicine (Dr Tykodi), and the Department of Pathology (Dr Fang), University of Washington, and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle. Drs Andeen and Qu contributed equally to this work.