Oncofetal (IMP3) and Stem Cell Markers in Primary and Metastatic Renal Cell Carcinoma
K Sher, P Rao, G Chen, MC Guoit, MA Fahmy, S Tanguay, K Aldape, K Sircar. McGill University Health Centre, Montreal, QC, Canada; MD Anderson Cancer Center, Houston, TX
Background: Clinicopathologic parameters are the mainstay for prognostication of most epithelial tumors, including renal cell carcinoma (RCC). Recently, stem cell markers and the oncofetal protein IMP3 have been proposed as conferring metastasizing potential to various carcinomas. The RNA binding oncofetal protein IMP3 has shown promise as a biomarker in primary RCC. We evaluated the expression of IMP3 as well as stem cell markers CD44, OCT 3/4, and CD133 in a set of primary and metastatic RCC.
Design: Tissue microarray sections were immunostained with antibody against IMP3, CD44, OCT 3/4 and CD133 on two distinct patient cohorts: A. Locally advanced (n=30) and organ confined (n=52) primary RCC; histology: 86% conventional/clear cell, 14% non-conventional; median follow up of 77 months; B. Metastatic RCC(n=136) with a subset of matched primary(n=26) tumors; histology: 95% conventional, 5% non-conventional; median follow up of 37 months. Immunohistochemistry on each core was scored as absent(0), weak(1+) or strong(2+). For statistical purposes, IMP3 staining was dichotomized as absent(0) or present(1+) as well. Computerized image analysis was also applied to the IMP3 stained sections.
Results: Among primary RCC, only IMP3 expression correlated with decreased metastasis free survival and overall survival (P=0.005). CD44, OCT 3/4 and CD133 were not prognostic. On multivariate analysis, however, IMP3 lost its independent prognostic value with only pathologic stage being significant (P=0.0004), regardless of how IMP3 was quantitated. None of the markers studied among metastatic lesions--including IMP3--correlated with survival.
Conclusions: Oncofetal IMP3 appears to have some value as a tissue biomarker in primary RCC whereas stem cell markers CD44, OCT 3/4 and CD133 do not. However, depending on the patient population studied, IMP3 may not be a significant predictor of adverse outcome independent of pathologic stage. It is also not prognostically useful in metastatic disease.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 143, Tuesday Afternoon