title: Molecular subtyping of metastatic renal cell carcinoma: implications for targeted therapy.
abstract: BACKGROUND
  Renal cell carcinoma (RCC) is known for its ability to metastasize synchronously or metachronously to various anatomic sites. Distinguishing histologic subtypes of metastatic RCC has become increasingly important, as prognosis and therapy can differ dramatically between subtypes. We propose a combination of immunohistochemistry (IHC) and molecular cytogenetics for subtyping metastatic RCC in light of these potential therapeutic implications.
  
  
  RESULTS
  Specimens from 103 cases of metastatic RCC were retrieved, including 32 cases originally diagnosed as metastatic clear cell renal cell carcinoma (CCRCC), 8 as metastatic papillary renal cell carcinoma (PRCC), and 63 metastatic RCC without a specific subtype. Immunohistochemistry was performed with antibodies against cytokeratin 7 (CK7) and alpha-methylacyl-CoA racemase (AMACR). Dual color interphase fluorescence in situ hybridization was utilized to assess for deletion of chromosome 3p and trisomy of chromosomes 7 and 17 in all tumors. Chromosome 3p deletion was detected in 41% of all metastatic RCC specimens, and trisomy of chromosomes 7 and/or 17 was detected in 16%. Of metastatic CCRCC, chromosome 3p deletion was detected in 63%. Of metastatic PRCC, 75% showed trisomy of chromosomes 7 and/or 17. Of the tumors not previously classified, 6% were positive for CK7, and 64% were positive for AMACR; 35% showed chromosome 3p deletion, and 16% showed trisomy of chromosomes 7 and/or 17. Combined analysis of immunohistochemistry and cytogenetics enabled reclassification of 52% of these metastatic tumors not previously classified.
  
  
  CONCLUSIONS
  Our findings support the utility of immunohistochemistry and cytogenetics for subtyping metastatic RCC.
authors.forename: Lisha
authors.initials: L
authors.lastname: Wang
authors.forename: Sean R
authors.initials: SR
authors.lastname: Williamson
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wang
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Davidson
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Baldridge
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. dx2008cn@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis
chemical_list: D014408:Biomarkers, Tumor