Clinicopathological Connotation of SOX2 Amplification and Expression in Urothelial Carcinoma
Somak Roy, Arivarasan Karunamurthy, Alyssa M Luvison, Marie B Acqafondata, Kathleen M Cieply, Anil V Parwani. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: SOX2, an oncogene, is expressed and amplified in squamous cell carcinoma (SCC) of the esophagus, lung and head and neck. Very recently, ALDH1 and SOX2 expression by immunohistochemistry (IHC) was reported in urothelial carcinoma (UC) of the upper urinary tract demonstrating negative prognostic implication. We attempted to investigate the expression and amplification status of SOX2 in the light of clinicopathologic parameters.
Design: A total of 19 consecutive radical cystectomy specimens with diagnosis of UC were retrieved from case archive after IRB approval. After review of H&E stained sections, targets were marked for fluorescence in-situ hybridization (FISH). Dual-color FISH for SOX2 was performed using clone RP11-43F17 (CHORI, Oakland, CA) labeled with Spectrum Orange (Abbott Molecular) and D3Z1 α-satellite labeled Spectrum Green (Cytocell aquarius, Cambridge, UK). Approximately 60 well delineated and non-overlapping cells were analyzed in the targeted region. IHC was performed using rabbit monoclonal antibody against SOX2 (Epitomics, Inc). IHC scoring was based on intensity of staining (1+ to 4+). For SOX2 positive staining, a minimum of 10% cells showed nuclear staining. A 4+ staining intensity was a surrogate for protein overexpression.
Results: The examined cohort had a M:F of 15:4 with mean age of 66.4 years. 89.5% (17/19) cases were diagnosed as high grade UC with four cases showing focal squamous and micropapillary features. The diagnosis of small cell carcinoma and micropapillary carcinoma comprised the remaining 2 cases. Overall, majority of UC showed very heterogeneous staining pattern of SOX2. 26% (5/19) cases demonstrated SOX2 overexpression (4+). In contrast SOX2 was amplified in only 21% (4/19) cases and 60% (3/5) cases with SOX2 overexpression. Interestingly, SOX2 was amplified in one case without SOX2 overexpression (2+). Amplification and expression did not correlate with T-stage, grade, tumor size and perineural invasion. Patients with SOX2 amplification demonstrated shorter median survival in contrast to SOX2 non-amplified cases (10.5 vs 15.5 months); difference of comparative magnitude was not seen in SOX2 expression patterns (13.1 vs 13.3 months).
Conclusions: Although SOX2 amplification and expression was seen in UC, there was a lack of concordance. SOX2 expression by IHC in UC should be interpreted with caution due to highly heterogeneous staining. SOX2 amplified cases appear to show shorter median survival than SOX2 non-amplified cases; further analysis using a larger cohort is under progress in our institution to test this hypothesis.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 153, Monday Morning