Oncofetal Proteins IMP3, Glypican-3 and TPBG Expression in Urothelial Carcinoma of the Bladder
Francesca Khani, Evanguelos Xylinas, Eugene Cha, Bjoern Volkmer, Luis Kluth, Douglas S Scherr, Mark A Rubin, Juan Miguel Mosquera, Richard E Hautmann, Rainer Kuefer, Shahrokh F Shariat, Brian D Robinson. Weill Cornell Medical College, New York, NY; University of Ulm, Ulm, Germany
Background: Oncofetal proteins comprise a group of immunogenic antigens that are normally expressed during fetal development but are aberrantly activated in a variety of malignancies, including urothelial carcinoma of the bladder (UCB). Previous studies have shown that oncofetal protein expression is more common in high-grade and advanced stage UCB. Insulin-like growth factor II mRNA-binding protein 3 (IMP3), glypican-3, and trophoblast glycoprotein (TPBG) are three oncofetal proteins that have not been well characterized in UCB. We investigated the expression of these three proteins and their association with pathologic features and clinical outcome in patients treated with radical cystectomy (RC).
Design: We utilized tissue microarrays (TMAs) containing samples from 383 consecutive UCB patients treated with RC between 1988 and 2003 at one academic center. Median follow-up was 129 months (IQR 111). The TMAs were stained using monoclonal antibodies against IMP3, glypican-3, and TPBG. Expression (absent vs. expressed) was evaluated by two pathologists who were blinded to clinical outcome.
Results: IMP3 was expressed in 39.4% (151/383) of malignant tissues from RC specimens. The rate of IMP3 expression increased with advancing pathological stage (p=0.02). Expression of IMP3 was associated with an increased risk of disease recurrence (p<0.001) and cancer-specific mortality (p=0.01). In a multivariable analysis that adjusted for the effects of pathologic stage and lymph node metastasis, IMP3 expression was independently associated with disease recurrence (HR 1.67, p=0.01), but not cancer-specific mortality. Glypican-3 and TPBG were expressed in 6.1% (19/311) and 85.6% (262/306) of tumors, respectively. Neither glypican-3 or TPBG were significantly associated with pathologic stage, disease recurrence, or cancer-specific survival on univariate or multivariate analysis.
Conclusions: IMP3 is expressed in ∼40% of high-risk UCB specimens at RC. IMP3 expression is associated with advanced pathologic tumor stage and disease recurrence in UCB patients treated with RC, while glypican-3 and TPBG are not. Further studies are needed to validate the clinical value of IMP3 as a prognostic biomarker and explore its role as a potential target for therapy in UCB.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 203, Tuesday Afternoon