Immunohistochemical Expression and Prognostic Value of ARID1A in Invasive Urothelial Carcinoma of Urinary Bladder
Sheila F Faraj, Nilda Gonzalez-Roibon, Alcides Chaux, Enrico Munari, Carla Ellis, Tina Driscoll, Mark P Schoenberg, Trinity Bivalacqua, Ie-Ming Shih, George J Netto. Johns Hopkins Hospital, Baltimore, MD; Norte University, Asuncion, Paraguay
Background: AT-rich interactive domain-containing protein 1A (ARID1A) is a tumor suppressor gene member of the chromatin remodeling genes family. Inactivation of ARID1A has been demonstrated in gynecologic malignancies. Only one study has previously addressed its status in bladder urothelial carcinoma (UC) showing inactivating mutations in less than one sixth of UC. Our study assesses the immunohistochemical expression of ARID1A in UC.
Design: Five tissue microarrays were constructed from 104 cystectomies performed in our institution for invasive UC (1994 to 2007). FFPE paired tumor and benign samples were spotted 3-4 times each. Immunohistochemistry was performed using a polyclonal rabbit anti-ARID1A (BAF250A) antibody (HPA005456, Sigma-Aldrich, St Louis, MO). H score representing the sum of nuclear staining intensity (0 to 3+) X extent (0%–100%) was calculated in each spot. Median H score per tumor was used during analysis. ARID1A expression was correlated with clinicopathologic features and overall survival (OS) and disease-specific survival (DSS). H-scores above the 4th quartile were considered as indicative of high expression.
Results: Median ARID1A H score was 264 (range:35-300). UC showed significantly higher expression than paired normal samples (P<0.001). ARID1A expression did not correlate with any of analyzed clinicopathologic features (gender, race, tumor stage, presence of lymph node or visceral metastasis). We found no statistically significant difference of expression between UC of usual and divergent differentiation (p=0.40). Median follow up was 34.5 months (range: 1-143 months). OS and DSS rates were 60% and 63%, respectively. We found a statistically significant association between ARID1A high expression and worse DSS (Mantel-Cox P=0.009). The latter was maintained on multivariate Cox regression analysis (HR=2.71, P=0.012). Although a trend for a negative prognostic impact of high ARID1A expression was noted for OS, the trend was not statistically significant (Mantel-Cox P=0.059).
Conclusions: ARID1A expression was higher in invasive UC compared to paired benign urothelium. ARID1A high expression was associated with worse DSS. The potentially protective effect for ARID1 inactivation on survival merits further evaluation in a larger cohort.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 163, Wednesday Afternoon