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Open Access 01-12-2014 | Research

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

Authors: Lisha Wang, Sean R Williamson, Mingsheng Wang, Darrell D Davidson, Shaobo Zhang, Lee Ann Baldridge, Xiang Du, Liang Cheng

Published in: Molecular Cancer | Issue 1/2014

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.

Conclusion

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

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Rao Q, Liu B, Cheng L, Zhu Y, Shi QL, Wu B, Jiang SJ, Wang Y, Wang X, Yu B, Zhang RS, Ma HH, Lu ZF, Tu P, Wang JD, Zhou XJ: Renal cell carcinomas with t(6;11)(p21;q12): A clinicopathologic study emphasizing unusual morphology, novel alpha-TFEB gene fusion point, immunobiomarkers, and ultrastructural features, as well as detection of the gene fusion by fluorescence in situ hybridization. Am J Surg Pathol. 2012, 36: 1327-1338. 10.1097/PAS.0b013e31825aafb5CrossRefPubMed

Title: Molecular subtyping of metastatic renal cell carcinoma: implications for targeted therapy
Authors: Lisha Wang
Sean R Williamson
Mingsheng Wang
Darrell D Davidson
Shaobo Zhang
Lee Ann Baldridge
Xiang Du
Liang Cheng
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-13-39

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