Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2005-7-4
pubmed:abstractText
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 G1-S and G2-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 IIalpha 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed-author:AmatoRobertR, pubmed-author:AnemaJohnJ, pubmed-author:BelldegrunArieA, pubmed-author:BettenMark WMW, pubmed-author:DitlevJonathon AJA, pubmed-author:FiglinRobertR, pubmed-author:FurgeKyle AKA, pubmed-author:FutamiKunihikoK, pubmed-author:KahnoskiRichardR, pubmed-author:KanayamaHiro-OmiHO, pubmed-author:KimHyung LHL, pubmed-author:KortEric JEJ, pubmed-author:LuanChunyanC, pubmed-author:NicolTheresaT, pubmed-author:PinsMichaelM, pubmed-author:RogersCraig GCG, pubmed-author:RospendaKathleen MKM, pubmed-author:SeligsonDavidD, pubmed-author:StadlerWalterW, pubmed-author:TakahashiMasayukiM, pubmed-author:TanMin-HanMH, pubmed-author:TanPuay HoonPH, pubmed-author:TehBin SingBS, pubmed-author:TehBin TeanBT, pubmed-author:TretiakovaMariaM, pubmed-author:VogelzangNicholas GNG, pubmed-author:YANGY TYT, pubmed-author:YangXiming JXJ
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5628-37
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
A molecular classification of papillary renal cell carcinoma.
pubmed:affiliation
Department of Pathology, Feinberg School of Medicine, Northwestern University, Illinois, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural