Open Access Open Badges Research

Molecular subtyping of metastatic renal cell carcinoma: implications for targeted therapy

Lisha Wang12, Sean R Williamson3, Mingsheng Wang2, Darrell D Davidson2, Shaobo Zhang2, Lee Ann Baldridge2, Xiang Du1* and Liang Cheng2*

Author Affiliations

1 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China

2 Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, IU Health Pathology Laboratory Room 4010, Indianapolis, IN 46202, USA

3 Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, MI, USA

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Molecular Cancer 2014, 13:39  doi:10.1186/1476-4598-13-39

Published: 26 February 2014



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.


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.


Our findings support the utility of immunohistochemistry and cytogenetics for subtyping metastatic RCC.

Kidney; Renal cell carcinoma; Metastasis; Targeted therapy; Molecular cytogenetics; Fluorescence in situ hybridization