Nuclear Expression of SOX9 Protein as a Prognostic Marker in Invasive Bladder Urothelial Carcinomas (UrCa): A Tissue Microarray Immunohistochemistry Study
TK Lee, R Albadine, S Jadallah, M Nielsen, SZ Ling, M Gonzalgo, DM Berman, GJ Netto. Johns Hopkins Hospital, Baltimore
Background: SOX9 is a transcription factor that plays an important role in cellular differentiation during embryogenesis. Recently alteration in SOX9 expression have been described in several types of solid tumors. The specific imunohistochemical expression pattern of SOX9 in UrCa and its prognostic significance has not been studied.
Design: TMAs were constructed from archival tissue from 138 consecutive cystectomies performed in our institution between 1994-2002. Triplicate tumor samples, corresponding benign urothelium and, when available, corresponding flat CIS were spotted from each cystectomy. Immunohistochemistry of SOX9 using a standard immunohistochemistry protocol and appropriate controls Intensity of SOX9 nuclear staining was evaluated and assigned an incremental 0,1+,2+,3+ score. Extent of staining was categorized as focal (<25% of cells), multifocal (25-75%), or diffuse (>75%). SOX9 score was generated for each tumor/benign as a product of intensity and distribution.
Results: Mean patient age at cystectomy was 63 yrs and M:F ratio was 4:1 w/ mean follow-up of 28 mos (1-106 mos). 7 patients were lost to follow-up. A total of 84 of 138 cases with evaluable UrCa were scored for SOX9. The latter included 60 cases of UrCa with favorable histology (UrCa, UrCa w/ focal glandular or squamous features) and 24 cases of UrCa with unfavorable histology (micropapillary, lymphoepithelial-like Ca, sarcomatoid Ca, adenoCa, signet-ring Ca, poorly differentiated Ca, squamous cell Ca). 34 paired normal urothelium cases were also scored. Our tumors were staged as pT1 (n=4), pT2 (n=28), pT3 (n=40) and pT4 (n=12). A higher SOX9 expression score was encountered in UrCa compared to paired benign tissue (mean score: 0.35). SOX9 tumor scores were significantly higher in the group of UrCa with unfavorable histology (mean score: 6.7) compared to UrCa with favorable histology (mean score: 4.2); p<0.005. Higher SOX9 scores were also significantly associated with higher pathologic stage (p<0.01). However, SOX9 expression did not predict with presence of lymph node metastasis, disease-free survival or overall survival in our cohort. (p:NS).
Conclusions: We found a higher SOX9 expression in UrCa tumors compared to benign controls. Higher SOX9 expression was found in tumors with unfavorable histology and those with more advanced stage suggesting a potential prognostic role in UrCa.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 125, Monday Morning