Cancer Stem Cell Marker Expression in Muscle-Invasive Urothelial Carcinoma.
Ed Diaz, Christina B Ching, Paul Elson, Donna E Hansel. Cleveland Clinic, OH
Background: Over the last decade, multiple cancer stem cell (CSC) markers have been identified, although few studies have evaluated the expression of these markers within urothelial carcinoma (UCC) or normal urothelium. In addition, few studies have correlated CSC marker expression with clinical outcome. Our objective was to assess known CSC marker expression in muscle-invasive UCC and benign urothelium and to determine effects on clinical outcome.
Design: A total of 118 UCC specimens and 21 benign urothelial specimens were processed into tissue microarrays and stained with commercial antibodies for CSC markers: CD15, CD24, CD44, CD44v6, CD47, CD67LR, CD117, OCT3/4. Tumors were considered positive if >5% of the cells demonstrated immunoreactivity and were then further substratified into focal or diffuse expression. The clinical course of patients with UCC was abstracted and clinical outcomes were correlated with CSC marker expression using statistical analysis.
Results: UCC specimens most commonly expressed diffuse immunoreactivity for CD24 (63%), CD44 (63%) and CD44v6 (69%), with co-expression of CD44 and CD44v6 in 50% of patients. CD67LR was diffusely expressed in 18% of cases, which corresponds to previously published data. Nuclear staining for OCT3/4 was present in only 5 cases (4%). No UCC specimen demonstrated immunoreactivity for the CSC markers CD47 or CD133. Evaluation of normal urothelium, in contrast, revealed only focal staining for CD24, CD44 and CD44v6 relative to carcinoma specimens (p<0.01) in 50%, 60% and 60% of normal cases, respectively. As in carcinoma specimens, CD44 and CD44v6 were co-expressed in 50% of cases. CD67LR was only expressed in 5% of normal specimens evaluated, but when present was diffusely expressed throughout the normal urothelium. Overall 35% of patients recurred (median recurrence-free survival 30.1 months) and 64% of patients died of disease (median survival 22.2 months). Analysis of recurrence-free and overall survival, when tiered for lymph node metastases, suggests that expression of CD67LR indicates an unfavorable prognosis in patients with lymph node metastases. Furthermore, specific combinations of CSC markers appear to impact outcomes.
Conclusions: CSC markers CD24, CD44, and CD44v6 appear to be expressed in higher percentages of UCC cells versus normal urothelium, suggesting a potential enrichment of CSCs in muscle-invasive UCC. Outcomes appear to be impacted by CD67LR in patients with lymph node metastases, as well as specific CSC marker combinations in patients with muscle-invasive UCC.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 188, Tuesday Morning