Expression of Toll-Like Receptors (TLRs) in Urothelial Carcinoma and Response to Bacillus Calmette-Guerin (BCG) Therapy
TM D'Alfonso, BD Robinson, EC Kaufman, DS Scherr. Weill Cornell Medical College, New York, NY; The Johns Hopkins Hospital, Baltimore, MD
Background: BCG is a widely used immunotherapy to treat non-invasive and superficially invasive bladder carcinoma. The anti-tumor effect of BCG is at least partially mediated through TLRs, a family of pattern recognition receptors that play an integral role in the defense against microorganisms. Recent studies have shown that TLRs are not restricted to immune-related cells, as previously suggested, but are also expressed in various epithelial cells and epithelial-derived tumors. In our study, we examine if expression of various TLRs in urothelial carcinoma is associated with response to BCG therapy.
Design: A tissue microarray of pTa, pTis, and pT1 urothelial carcinomas was created from 59 transurethral resections of the bladder (TURB) from 51 patients. All TURB specimens were taken prior to BCG therapy. Immunohistochemical staining for TLR7 and TLR9 was performed. Each tumor was given two scores – one score based on the percentage of tumor cells staining (no cells=0; <10%=1; 10-75%=2; >75%=3), and one score based on staining intensity (1=weak; 2=moderate; 3=strong).
Results: Thirty-six tumors were BCG-responsive, while 23 tumors were classified as BCG-failures. The mean %-cell positive score for TLR7 in the BCG-responsive tumors (2.3) was significantly greater than that for tumors not responsive to BCG therapy (1.8; p<0.05). No significant difference was seen regarding the intensity of TLR7 staining between the two groups. TLR9 expression was not significantly different with respect to percentage of cells positive; however, the staining intensity, regardless of %-positive cells, was significantly stronger in BCG-responsive tumors compared to BCG non-responders (1.2 versus 0.77, respectively; p<0.05). Neither TLR7 nor TLR9 showed any correlation with tumor stage. Additionally, within the non-invasive papillary tumors (pTa), no significant difference in TLR staining was seen with respect to tumor grade (high versus low).
Conclusions: These preliminary results show an association between TLR expression in urothelial carcinoma and response to BCG therapy, and they support the role of TLRs in the mediation of BCG response. Further investigation ongoing in our laboratory, including examination of TLRs 2, 4, and 8, may show that the evaluation of TLR expression is a useful tool for urologists when contemplating the utility of BCG for individual patients.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 149, Wednesday Afternoon