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Mutations in the von Hippel‐Lindau (VHL) gene refine differential diagnostic criteria in renal cell carcinoma
Author(s) -
Barnabas Nandita,
Amin Mitual B.,
Pindolia Kirit,
Nanavati Reshma,
Amin Mahul B.,
Worsham Maria J.
Publication year - 2002
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.10086
Subject(s) - medicine , von hippel–lindau disease , renal cell carcinoma , differential diagnosis , gene , carcinoma , cancer research , pathology , oncology , genetics , biology , disease
Background and Objectives Renal cell carcinomas (RCC) with abundant granular cytoplasm include oncocytomas, eosinophillic variants of chromophobe RCC, papillary RCC, collecting duct carcinoma, and some conventional (clear cell) RCC. Tumors with predominantly clear cell cytoplasm include typical chromophobe RCC and conventional (clear cell) RCC. The objective of this study was to determine if mutations in the VHL gene can serve as auxiliary diagnostic criteria in refining histology based subtyping of renal epithelial neoplasia. Methods The study cohort of 67 cases included 24 conventional RCC, 14 chromophobe RCC, 14 papillary RCC, and 15 oncocytomas. Single strand conformational polymorphism (SSCP) was used as a screening procedure for mutations followed by automated sequencing to identify mutations. Results Thirteen of the 14 mutations identified were novel, seven of which were in the coding region. In chromophobe RCC, mutations clustered in the 5′UTR/promoter region and have not been previously reported. Exon 3 appeared to favor conventional (clear cell) RCC and correlated with a more aggressive phenotype. Mutations were absent in the papillary and oncocytoma RCC subtypes. Conclusions Exon 3 mutations permitted a morphological distinction between conventional (clear cell) RCC and chromophobe RCC with clear cells. Mutations in the VHL gene refine histologic diagnostic criteria in RCC serving as adjuncts to the present morphology based diagnosis of RCC. J. Surg. Oncol. 2002;80:52–60. © 2002 Wiley‐Liss, Inc.