Evaluation and Significance of S100A4 Expression in Renal Neoplasms
K Sciandra, E Sabo, M Lechpammer, P Meitner, Y Zhang, R Tavares, L Noble, R DeLellis, MB Resnick, LJ Wang. Rhode Island Hospital and the Alpert Brown University Medical School, Providence, RI
Background: S100 proteins are a family of calcium binding proteins, which have been implicated in various intracellular and extracellular functions ranging from the control of cell-cycle progression, cell differentiation, extracellular signaling, cell motility, signal transduction, and intercellular adhesion to invasion and metastasis. Overexpression of S100A4 has been associated with progression and poor clinical outcome in a variety of malignancies such as breast, pancreas, bladder and thyroid carcinomas. There have been conflicting reports on the expression of S100A4 in the kidney. In this study we evaluated the expression of S100A4 protein and mRNA in the normal kidney and renal neoplasms and correlated S100A4 expression with patient outcome.
Design: Tissue microarrays were created from archival paraffin-embedded tissue samples from 203 patients with renal cell neoplasms. The arrays included 155 clear cell (cRCC), 22 papillary (pRCC) and 13 chromophobe (chRCC) carcinomas as well as 13 oncocytomas (OC). The microarrays were immunohistochemically stained with an S100A4 polyclonal antibody (Dako). In addition, S100A4 mRNA was quantified by RT-PCR on frozen tissue samples of 20 cRCC, 4 pRCC, 3 OC and 3 chCC.
Results: Results: Nuclear and cytoplasmic S100A4 staining was detected in the glomerular epithelium and endothelium, distal tubules, collecting ducts and loops of Henle, with no or weak staining of the proximal tubules. A differential expression pattern was demonstrated between the various neoplasms. Positive staining was more common in pRCC (58%) than cRCC (11%) (P=0.01) whereas there was stronger S100A4 expression in chRCC (62%) than in OC (17%) (P = 0.04). The level of mRNA detected by RT-PCR were significantly higher in tumor as opposed to normal tissue in cRCC but not in the other neoplasms (15.4 vs 8.2 relative units, P= 0.03). Univariate and multivariate survival analysis revealed that S100A4 protein expression is an independent poor prognostic factor along with grade and stage in cRCC (p<0.01).
Conclusions: S100A4 expression is increased in all renal neoplasms and parallels the expression pattern seen in their histogenetic cells of origin from the normal kidney. Despite its relatively lower frequency of expression in cRCC, S100A4 was shown to be a poor prognostic factor in cRCC by both univariate and multivariate analysis.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 75, Tuesday Morning