Comparison of Gene Expression Profiles in Tubulocystic Carcinoma and Collecting Duct Carcinoma of the Kidney
AO Osunkoya, AN Young, W Wang, GJ Netto, JI Epstein. Emory University School of Medicine, Atlanta, GA; Ohio State University, Columbus, OH; The Johns Hopkins Hospital, Baltimore, MD
Background: The relationship between tubulocystic carcinoma (TCCa) and collecting duct carcinoma (CDC) of the kidney remains controversial. Some experts believe that the tumors are related, considering TCCa to be synonymous with low grade CDC. However, others maintain that the two are distinct, unrelated entities based on morphologic features and clinical outcome. In addition, recent reports suggest a distinct immunohistochemical (IHC) phenotype for TCCa, which may be useful for distinguishing this lesion from CDC and other renal tumor subtypes. To explore the relationship between TCCa and CDC, we compared the expression of several gene products at the mRNA level in cohorts of each tumor subtype.
Design: Seven cases of TCCa and eight cases of CDC were identified. Total RNA was isolated from formalin-fixed paraffin-embedded tissue from each case. Relative expression levels of vimentin, alpha methylacyl coA racemase (AMACR), E-cadherin, p53, CD10, cytokeratin 7 (CK7) and cytokeratin 19 (CK19) were assessed by quantitative RT-PCR. We selected these genes in light of recent immunohistochemical studies of TCCa, as well as previous differential expression data generated by our laboratory.
Results: TCCa were characterized by relative overexpression of vimentin, p53 and AMACR, compared to CDC (p<0.05 for each gene, T-Test). In general, TCCa expressed higher levels of E-cadherin and CD10, while CDC expressed higher levels of CK19; however, these trends did not reach statistical significance in this study cohort. TCCa and CDC did not express CK7 differentially. Case-to-case variability of gene expression limited the effectiveness of any one marker to distinguish the tumor types.
Conclusions: Our study demonstrates that TCCa and CDC have different expression profiles of selected genes, including vimentin, p53 and AMACR. Further analysis of additional cases, using quantitative RT-PCR and IHC, will be useful to test the reproducibility of these findings. In addition, larger studies may establish statistical differences in expression of other genes analyzed in this study. Overall, these findings support the view that TCCa and CDC should be considered as two distinct entities at the molecular level.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 83, Tuesday Morning