A molecular classification of papillary renal cell carcinoma

Ximing J. Yang, Min Han Tan, Hyung L. Kim, Jonathon A. Ditlev, Mark W. Betten, Carolina E. Png, Eric J. Kort, Kunihiko Futami, Kyle A. Furge, Masayuki Takahashi, Hiro Omi Kanayama, Puay Hoon Tan, Bin Sing Teh, Chunyan Luan, Kim Wang, Michael Pins, Maria Tretiakova, John Anema, Richard Kahnoski, Theresa NicolWalter Stadler, Nicholas G. Vogelzang, Robert Amato, David Seligson, Robert Figlin, Arie Belldegrun, Craig G. Rogers, Bin Tean Teh

Research output: Contribution to journalArticlepeer-review

204 Scopus citations


Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is a disproportionately limited understanding of its underlying genetic programs. There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials. A morphologic classification of PRCC into type 1 and 2 tumors has been recently proposed, but its biological relevance remains uncertain. We studied the gene expression profiles of 34 cases of PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both unsupervised and supervised analyses. Comparative genomic microarray analysis was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples with 15 independent tumors. We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histologic subtypes: type 1, low-grade type 2, and mixed type 1/low-grade type 2 tumors. The second class, with poor survival, corresponded to high-grade type 2 tumors (n = 11). Dysregulation of G 1-S and G 2-M checkpoint genes were found in class 1 and 2 tumors, respectively, alongside characteristic chromosomal aberrations. We identified a seven-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in class 1 tumors and of topoisomerase IIα in class 2 tumors. We report two molecular subclasses of PRCC, which are biologically and clinically distinct and may be readily distinguished in a clinical setting.

Original languageEnglish (US)
Pages (from-to)5628-5637
Number of pages10
JournalCancer research
Issue number13
StatePublished - Jul 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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