Expression of EMT Markers in Sarcomatoid Urothelial Carcinoma of the Bladder
Joseph M Sanfrancesco, Sounak Gupta, Aaron Shoskes, Greg Lieser, Donna Hansel. Cleveland Clinic Foundation, Cleveland, OH
Background: The sarcomatoid variant of urothelial carcinoma (UCa) of the urinary bladder is one of several rare, aggressive variants that have posed challenges for clinicians in determining prognosis and treatment. Epithelial-to-mesenchymal transition (EMT) has been described to occur in instances in which tumors develop increased motility and propensity to spread; this phenomenon has been associated with the development of a spindled morphology in multiple in vitro settings. We therefore explored the expression of EMT markers in sarcomatoid UCa – a highly aggressive variant of UCa that is characterized by a spindled, mesenchymal-like appearance.
Design: We compiled 26 cases of sarcomatoid UCa diagnosed at our institution between the years 2000 to 2012. The cases consisted of biopsies (n=3), transurethral resections (n=3), and radical cystectomy /cystoprostatectomies (n=20). A tissue microarray (TMA) containing multiple representations of each tumor was constructed and stained for N-cadherin (Ventana, 1:200 dilution), B-catenin (BD-Biosciences, 1:250 dilution), pS6 (Ventana, 1:25 dilution), Vimentin (Ventana, 1:100 dilution), ZEB1 (Ventana, 1:100 dilution), FoxC2 (Ventana, 1:25 dilution), E-cadherin (Invitrogen, 1:250 dilution), and SNAIL/SL (Ventana, 1:50 dilution). Interpretation of immunohistochemical (IHC) staining was completed using a 0-3 scale, with most prominent expression, based on intensity, being classified at 3 and no expression being classified as 0.
Results: Of the 26 patients utilized in this study, 15 were men and 11 were women (M:F ratio = 1.4) ranging from 42-92 years of age. IHC staining of ≥ 2 was considered positive and was diffusely and uniformly expressed in the neoplastic cells with sarcomatoid features. Vimentin and FoxC2 were positive in all cases, and positive staining for SNAIL/SL and B-catenin was 88.5% (23/ 26) and 80.8% (21/26) respectively. E-cadherin showed a positive staining pattern in only 4 of 26 cases (15.4%). ZEB1, pS6, and N-cadherin showed mixed patterns of positivity with 80.1% (18/26), 53.8% (14/26), and 46.2% (12/26), respectively.
Conclusions: Sarcomatoid UCa of the bladder appears to demonstrate consistent properties of EMT, including loss of E-cadherin expression and increased Vimentin and SNAIL/SL expression. Variable staining for additional EMT markers, such as ZEB1, pS6 and N-cadherin, remains to be explored in more detail. Ultimately, in vitro and in vivo functional studies that demonstrate alteration in behavior associated with EMT marker expression will be required to demonstrate the relationship between phenotype and tumor cell behavior.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 202, Tuesday Afternoon