YKL-40 as a Marker of Epithelial to Mesenchymal Transition in Primary and Metastatic Renal Cell Carcinoma
P Rao, P Tamboli, S Tanguay, KD Aldape, K Sircar. MD Anderson Cancer Center, Houston, TX; McGill University Health Centre, Montreal, QC, Canada
Background: The process of epithelial mesenchymal transition (EMT), whereby epithelial cells acquire a more motile mesenchymal phenotype with the potential to break down extracellular matrix and invade into vessels, is now emerging as a common mechanism for invasion across many tumors. Renal cell carcinomas (RCC) are known to show a histologic correlate of EMT in the form of sarcomatoid RCC that shows a spindle cell, mesenchymal morphology and behaves very aggressively. YKL-40 is a secreted protein implicated in physiologic and neoplastic EMT and whose serum levels have been correlated to poorer prognosis in various solid tumors. We examined the tissue expression of this protein in primary, metastatic and sarcomatoid RCC.
Design: Tissue microarray sections were immunostained with antibody against YKL-40 on three distinct patient cohorts: A. Sarcomatoid RCC (n=25); B. High risk (pT3b, n=30), and low risk (pT1a, n=52) primary RCC; histology: 86% conventional/clear cell, 14% non-conventional; median follow up 77 months; C. Metastatic RCC( n=136) with a subset of matched primary(n=26) tumors; histology: 95% conventional, 5% non-conventional; median follow up 37 months. Immunohistochemistry on each core was scored as absent(0), weak(1+) or strong(2+).
Results: All sarcomatoid RCC showed strong (2+) immunoreactivity for YKL-40 confirming its mesenchymal phenotype. Primary RCC showed increased YKL-40 (mean:1.59, 63% 2+) compared to their matched metastases(mean: 1.33, 39% 2+), P=0.036. Among primary high and low risk RCC, YKL-40 expression did not show a significant association with either metastasis free survival or overall survival. However, a trend toward increased disease specific mortality was seen with increased YKL-40 expression in metastatic lesions, P=0.077.
Conclusions: YKL-40 expression is a marker of mesenchymal differentiation in RCC and a potential therapeutic target in this disease. Its downregulation at metastatic sites suggests that transition from an epithelial to a mesenchymal phenotype is largely operational at the site of the primary tumor. Tissue levels of YKL-40 do not appear to be prognostically significant in RCC.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 111, Wednesday Afternoon