Cancer/Testis (CT) Antigen Expression Correlates with Non-Response to BCG Therapy and Invasive Disease in Human Bladder Cancers.
Brian D Robinson, Timothy M D'Alfonso, Rita Chiu, Eric C Kauffman, Douglas S Scherr, Lloyd J Old, Yao-Tseng Chen. Weill Cornell Medical College, New York; Ludwig Institute for Cancer Research, New York
Background: CT antigens comprise a group of immunogenic proteins normally expressed only in germ cells but aberrantly activated in a variety of cancers, including urothelial carcinoma. Previous studies have shown that CT antigen expression is more common in high grade bladder tumors, and some CT antigens have been shown to weakly correlate with pathologic stage. Given the likely role of the immune system in the effectiveness of Bacillus Calmette-Guérin (BCG) therapy in superficial urothelial carcinoma, we investigated whether CT antigen expression would correlate with BCG therapy response. Possible correlations between CT antigen expression, tumor invasion (pTa/Tis v. pT1) and p53 expression were also examined.
Design: Protein expression of 7 CT antigens (MAGEA, NY-ESO-1, CT7, CT10, CT45, GAGE, SAGE1) and p53 was immunohistochemically evaluated in a tissue microarray containing 125 urothelial carcinoma samples in triplicate from 78 BCG-treated patients (32 pTa, 11 pTis, 35 pT1). Pre- and post-BCG samples were available in 16 patients, pre-BCG only in 37, and post-BCG only in 25 patients. For CT antigens, unequivocal nuclear or cytoplasmic staining in any tumor cells was considered positive. Only nuclear staining was considered positive for p53.
Results: CT antigen positivity strongly correlated with invasive disease (any CT+ seen in 60% of pT1 v. 23% of pTa/Tis; p=0.001) and also correlated with non-response to BCG immunotherapy (p=0.03). Invasive carcinomas (pT1) showed a trend toward BCG failure when compared to non-invasive tumors (pTa/Tis; p=0.06). In the 16 cases with both pre- and post-BCG samples, no change was seen in CT antigen expression before and after treatment. CT antigen positivity correlated with p53 overexpression (p=0.03); however, p53 positivity did not correlate with BCG response.
Conclusions: Expression of any CT antigen correlates with BCG failure. One explanation may be that CT antigens are more frequently expressed in invasive tumors, a group less likely to respond to BCG treatment than non-invasive tumors in our cohort. Alternatively, it may be that CT+ tumors, already presenting "foreign" antigens to the immune system and escaping cell death, are likewise impervious to the immunomodulatory effects of BCG instillation. Our findings suggest that CT antigen expression may be useful in deciding whether to treat a patient with BCG or a more aggressive therapy. CT antigen expression may also help identify those non-invasive tumors at high risk for progression to invasion.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 178, Tuesday Morning