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  • Oncogenomics
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Molecular subclassification of kidney tumors and the discovery of new diagnostic markers

Oncogene volume 22, pages 6810–6818 (2003)Cite this article

Abstract

We analysed the expression profiles of 70 kidney tumors of different histological subtypes to determine if these subgroups can be distinguished by their gene expression profiles, and to gain insights into the molecular mechanisms underlying each subtype. In all, 39 clear cell renal cell carcinomas (RCC), seven primary and one metastatic papillary RCC, six granular RCC from old classification, five chromophobe RCC, five sarcomatoid RCC, two oncocytomas, three transitional cell carcinomas (TCC) of the renal pelvis and five Wilms' tumors were compared with noncancerous kidney tissues using microarrays containing 19 968 cDNAs. Based on global gene clustering of 3560 selected cDNAs, we found distinct molecular signatures in clear cell, papillary, chromophobe RCC/oncocytoma, TCC and Wilms' subtypes. The close clustering in each of these subtypes points to different tumorigenic pathways as reflected by their histological characteristics. In the clear cell RCC clustering, two subgroups emerged that correlated with clinical outcomes, confirming the potential use of gene expression signatures as a predictor of survival. In the so-called granular cell RCC (terminology for a subtype that is no longer preferred), none of the six cases clusters together, supporting the current view that they do not represent a single entity. Blinded histological re-evaluation of four cases of ‘granular RCC’ led to their reassignment to other existing histological subtypes, each compatible with our molecular classification. Finally, we found gene sets specific to each subtype. In order to establish the use of some of these genes as novel subtype markers, we selected four genes and performed immunohistochemical analysis on 40 cases of primary kidney tumors. The results were consistent with the gene expression microarray data: glutathione S-transferase α was highly expressed in clear cell RCC, α methylacyl racemase in papillary RCC, carbonic anhydrase II in chromophobe RCC and K19 in TCC. In conclusion, we demonstrated that molecular profiles of kidney cancers closely correlated with their histological subtypes. We have also identified in these subtypes differentially expressed genes that could have important diagnostic and therapeutic implications.

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Acknowledgements

We thank the Laboratory of DNA and Protein Microarray technology at Van Andel Research Institute (VARI) and Can Gong at the University of Chicago for their technical assistance. We want to acknowledge the contribution of some of the tumors studied by the Cooperative Human Tissue Network (CHTN). We also thank members of the Grand Rapids Urology Study Group including Ken Shockley, John Ludlow, David Kracklau, Philip Wise, Brian Roelof, Jon Curry and pathologists at the Spectrum Health and Metropolitan Hospitals. Finally, we thank Vivve Howell and Rick Hay for kindly reviewing the manuscript.

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Authors and Affiliations

  1. Laboratory of Cancer Genetics, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, 49503, MI, USA

    Masayuki Takahashi, Jun Sugimura, Jesper Backdahl, Chao-Nan Qian, Steven G Gray & Bin Tean Teh

  2. Department of Urology, School of Medicine, The University of Tokushima, Tokushima, 770-8503, Japan

    Masayuki Takahashi

  3. Department of Pathology, University of Chicago, 5841 South Maryland Avenue, Chicago, 60637, IL, USA

    Ximing J Yang & Maria Tretiakova

  4. Department of Surgery/Urology, University of Chicago, 5841 South Maryland Avenue, Chicago, 60637, IL, USA

    Ximing J Yang & Nicholas J Vogelzang

  5. Department of Pathology, Spectrum Health Hospital, Michigan St, NE, Grand Rapids, 49503, MI

    Robert Knapp

  6. Division of Urology, Spectrum Health Hospital, Michigan St NE, Grand Rapids, 49503, MI, USA

    John Anema & Richard Kahnoski

  7. Department of Urology, Princess Alexandra Hospital, Queensland, 4102, Australia

    David Nicol

  8. Department of Medicine, University of Chicago, 5841 South Maryland Avenue, Chicago, 60637, IL, USA

    Nicholas J Vogelzang

  9. Bioinformatics Program, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, 49503, MI, USA

    Kyle A Furge

  10. Department of Urology, School of Medicine, The University of Tokushima, Tokushima, 770-8503, Japan

    Hiroomi Kanayama & Susumu Kagawa

  11. Department of Urology, School of Medicine, Iwate medical University, Morioka, 020-8505, Japan

    Jun Sugimura

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  1. Masayuki Takahashi
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Correspondence to Bin Tean Teh.

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Takahashi, M., Yang, X., Sugimura, J. et al. Molecular subclassification of kidney tumors and the discovery of new diagnostic markers. Oncogene 22, 6810–6818 (2003). https://doi.org/10.1038/sj.onc.1206869

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