Chromosomal imbalances in papillary renal cell carcinoma: genetic differences between histological subtypes.

Papillary renal-cell carcinoma (RCC) is a renal carcinoma variant with distinct gross, microscopic, and cytogenetic features. Recently, a type 1 (pale cytoplasm, small-cell) and a type 2 (eosinophilic cytoplasm, large-cell) subtype of papillary RCC have been described. Chromosomal alterations associated with these tumor types were examined in 25 papillary RCCs by comparative genomic hybridization. Relative copy number gains were frequently detected at chromosomes 7p (56%), 7q (44%), 12q (28%), 16q (32%), 17p (56%), 17q (76%), and 20q (32%). Chromosomal regions that were most often lost included 1p (24%), 4q (36%), 6q (40%), 9p (36%), 13q (36%), Xp (28%), Xq (36%), and Y (73%). There were clinical and genetic differences between the subtypes of papillary RCC. Type 2 tumors were of higher nuclear grade (P = 0.0012) and higher stage (P = 0.01) and had a worse prognosis (P = 0.03) than type 1 tumors. The number of DNA gains per tumor, especially gains of 7p and 17p, was significantly higher in type 1 than in type 2 tumors (P < 0.01). These data suggest the existence of two distinct morphological and genetic subgroups of papillary RCC. Losses of chromosome Xp were associated with short patient survival (P < 0.01). Despite the small number of cases, this finding suggests that a gene on chromosome Xp may contribute to papillary RCC progression.

[1]  W. Linehan,et al.  Chromosome imbalances in papillary renal cell carcinoma and first cytogenetic data of familial cases analyzed by comparative genomic hybridization. , 1996, Cytogenetics and cell genetics.

[2]  H. Aburatani,et al.  Papillary Renal Cell Carcinoma: Quantitation of Chromosomes 7 and 17 by FISH, Analysis of Chromosome 3p for LOH, and DNA Ploidy , 1996, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[3]  G. Kovacs,et al.  Cytogenetics of papillary renal cell tumors , 1991, Genes, chromosomes & cancer.

[4]  J. Batsakis,et al.  PCR‐Based RFLP Screening of the Commonly Deleted 3p Loci in Renal Cortical Neoplasms , 1993, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[5]  B. Delahunt,et al.  Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors. , 1997, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[6]  H. Moch,et al.  Comparative genomic hybridization reveals frequent chromosome 13q and 4q losses in renal carcinomas with sarcomatoid transformation , 1998, Journal of Pathology.

[7]  E. Avner,et al.  The severe perinatal form of autosomal recessive polycystic kidney disease maps to chromosome 6p21.1-p12: implications for genetic counseling. , 1995, American journal of human genetics.

[8]  J. Brooks,et al.  Tumor suppressor gene allelic loss in human renal cancers. , 1993, The Journal of urology.

[9]  S. Bonsib,et al.  Papillary renal tumors. Morphologic, cytochemical, and genotypic features , 1995, Cancer.

[10]  J. Chudek,et al.  Loss of heterozygosity at chromosomes 8p, 9p, and 14q is associated with stage and grade of non‐papillary renal cell carcinomas , 1997, The Journal of pathology.

[11]  G. H. Weiss,et al.  Molecular analysis of genetic changes in the origin and development of renal cell carcinoma. , 1991, Cancer research.

[12]  P. Bugert,et al.  Molecular differential diagnosis of renal cell carcinomas by microsatellite analysis. , 1996, The American journal of pathology.

[13]  A. Renshaw,et al.  Solid variants of papillary (chromophil) renal cell carcinoma: clinicopathologic and genetic features. , 1997, The American journal of surgical pathology.

[14]  J. Brooks,et al.  Mutations of the VHL tumour suppressor gene in renal carcinoma , 1994, Nature Genetics.

[15]  P. Goodfellow,et al.  A pseudoautosomal gene in man. , 1986, Science.

[16]  H. Weier,et al.  Clonal aberrations of chromosomes x, y, 7 and 10 in normal kidney tissue of patients with renal cell tumors , 1992, Genes, chromosomes & cancer.

[17]  M. Hughson,et al.  Nonpapillary and papillary renal cell carcinoma: a cytogenetic and phenotypic study. , 1993, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[18]  W. Benedict,et al.  Loss of retinoblastoma gene function and heterozygosity at the RB locus in renal cortical neoplasms. , 1997, Human pathology.

[19]  P. Goodfellow,et al.  The mammalian pseudoautosomal region. , 1989, Trends in genetics : TIG.

[20]  S. Jhanwar,et al.  Histopathological, cytogenetic, and molecular characterization of renal cortical tumors. , 1991, Cancer research.

[21]  R. Greenberg,et al.  Comprehensive allelotyping of human renal cell carcinomas using microsatellite DNA probes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[22]  F. Waldman,et al.  EGF‐r gene copy number changes in renal cell carcinoma detected by fluorescence in situ hybridization , 1998, The Journal of pathology.

[23]  H. Willard,et al.  Localization of a gene that escapes inactivation to the X chromosome proximal short arm: implications for X inactivation. , 1990, American journal of human genetics.

[24]  P. Yen,et al.  Physical mapping of loci in the distal half of the short arm of the human X chromosome: Implications for the spreading of X-chromosome inactivation , 1992, Somatic cell and molecular genetics.

[25]  G. Kovacs.  Papillary renal cell carcinoma. A morphologic and cytogenetic study of 11 cases. , 1989, The American journal of pathology.

[26]  C. Junien,et al.  Report of the committee on chromosome and gene loss in human neoplasia , 1991 .

[27]  D. Schaid,et al.  Tumor necrosis factor-α allelic frequency and chromosome 6 allelic imbalance in patients with colorectal cancer , 1996 .

[28]  S. Fuhrman,et al.  Prognostic significance of morphologic parameters in renal cell carcinoma , 1982, The American journal of surgical pathology.

[29]  R. Greenberg,et al.  Genomic alterations and instabilities in renal cell carcinomas and their relationship to tumor pathology. , 1995, Cancer research.

[30]  F. Waldman,et al.  Genetic aberrations detected by comparative genomic hybridization are associated with clinical outcome in renal cell carcinoma. , 1996, Cancer research.

[31]  E. van den Berg,et al.  Cytogenetic analysis of epithelial renal‐cell tumors: Relationship with a new histopathological classification , 1993, International journal of cancer.

[32]  T C Gasser,et al.  Intratumoral heterogeneity of von Hippel-Lindau gene deletions in renal cell carcinoma detected by fluorescence in situ hybridization. , 1998, Cancer research.

[33]  D. Pinkel,et al.  Comparative Genomic Hybridization for Molecular Cytogenetic Analysis of Solid Tumors , 2022 .

[34]  R. Stanley,et al.  Papillary renal cell carcinoma. A clinical, radiologic, and pathologic study of 34 cases , 1976, Cancer.

[35]  J. Weissenbach,et al.  Physical mapping of the human pseudo‐autosomal region; comparison with genetic linkage map. , 1988, The EMBO journal.

[36]  C. Cordon-Cardo,et al.  Allelic deletions in renal tumors: histopathological correlations. , 1993, Cancer research.

[37]  A. Renshaw,et al.  Papillary (chromophil) renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 62 cases. , 1997, The American journal of surgical pathology.

[38]  C. Buys,et al.  Loss of heterozygosity at the short arm of chromosome 3 in renal‐cell cancer correlates with the cytological tumour type , 1993, International journal of cancer.

[39]  K. Zerres,et al.  Fine mapping of MEP1A, the gene encoding the alpha subunit of the metalloendopeptidase meprin, to human chromosome 6P21. , 1995, Biochemical and biophysical research communications.

[40]  H. Moch,et al.  Marked genetic differences between stage pTa and stage pT1 papillary bladder cancer detected by comparative genomic hybridization. , 1997, Cancer research.