MAGE-A Expression Is Associated with Features of Biologically Aggressive Urothelial Carcinoma of the Bladder
Francesca Khani, Eugene K Cha, Bjoern Volkmer, Michael Rink, Yao T Chen, 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; Klinikum Kassel, Kassel, Germany; Hospital Ulm, Ulm, Germany
Background: Cancer/Testis (CT) antigens comprise a group of immunogenic proteins that are normally expressed only in germ cells but are aberrantly activated in a variety of malignancies, including urothelial carcinoma of the bladder (UCB). MAGE-A, a member of the CT multigene family, is believed to encode a transcriptional regulator that potently inhibits p53 function. Previous studies have shown that CT antigen expression, including MAGE-A, is more common in high-grade and advanced stage UCB. We sought to further elucidate the association of MAGE-A expression with pathologic features of UCB and clinical outcomes of patients treated with radical cystectomy (RC).
Design: We evaluated a tissue microarray (TMA) containing samples from 361 consecutive UCB patients treated with RC between 1988 and 2003 at one academic center. In addition, 16 normal urothelium, 49 corresponding TUR specimens, and 92 corresponding lymph node (LN) metastases were analyzed. MAGE-A immunohistochemical staining was performed using a monoclonal antibody (6C1). Semi-quantitative MAGE-A expression was evaluated by two pathologists who were blinded to clinical outcome.
Results: MAGE-A was expressed in 152/361 (42.1%) RC-specimens, 20/49 (40.8%) TUR-specimens, and 38/92 (41.3%) LN metastases. No staining in benign urothelium was observed. MAGE-A expression was significantly associated with advanced clinical stage (p=0.01), pathological tumor stage (Ta/Tis=0%, T1=26%, T2=43%, T3=43%, T4=51%; p=0.02), and presence of lymph node metastasis (LN– 38% vs. LN+ 49%; p=0.04) but not tumor grade (p=0.25). After adjusting for the effects of established pathological features (stage, grade, LN metastasis), MAGE-A expression was not associated with disease recurrence (p=0.56) or cancer-specific mortality (p=0.56) at a median follow-up of 130 months. High concordance in MAGE-A expression between corresponding RC and TUR specimens (75%, p<0.001) and between corresponding RC and LN metastases (88%; p<0.001) was observed.
Conclusions: MAGE-A is expressed in >40% of high-risk UCB specimens at RC, and its expression is associated with advanced pathologic tumor stage and presence of LN metastases. Thus, MAGE-A expression, in combination with additional biomarkers, may identify patients with biologically aggressive disease and aid in selecting candidates for neoadjuvant chemotherapy. Incorporation of MAGE-A staining within a panel of other prognostic biomarkers is currently underway in this cohort.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 80, Tuesday Afternoon