Background: Cancer/testis antigens (CTA) are expressed in urothelial bladder cancer (UBC). Their therapeutical and prognostic relevance remains unclear. We studied the correlation of MAGEA3 and CTAG1B with histopathological factors in UBC and their prognostic value. Methods: Retrospective analysis of 93 patients who underwent treatment for UBC was conducted. Besides clinical and histopathological parameters, the expression of MAGEA3 and CTAG1B was assessed by immunohistochemistry. Results: Median follow-up was 75 months. Fifteen per cent of patients showed strong positive reaction to MAGEA3 staining. These tumours were statistically and significantly more often correlated with unfavourable World Health Organization (WHO) grading (G1: 0%, G2: 10.3%, G3: 23.4%, p = 0.048; low grade 0%, high grade 18.4%, p = 0.046 respectively). Correlation of CTAG1B with WHO grading was impressive with strong expression in no G1, 31.1% of G2 and 51.1% of G3 tumours (low grade 0%, high grade 43.4%, p = 0.001, respectively). Concomitant carcinoma in situ (Cis) was associated with strong CTAG1B expression (54.2% in concomitant Cis vs. 29% without concomitant Cis, p = 0.026). Kaplan-Meier analysis revealed statistically and significantly worse 5 years progression-free survival (PFS) associated with a strong expression of MAGEA3 (59 vs. 84%, p = 0.032). Conclusions: Strong CTA expression was correlated with unfavourable histopathological features. A strong expression of MAGEA3 was statistically and significantly associated with worse PFS across all stages of UBC.

Keywords:
Bladder, Cancer, Prognostic factors, Cancertestis antigens , CTAG1B, NY-ESO1, MAGEA3
1.
Schmitz-Drager BJ, et al: Molecular markers for bladder cancer screening, early diagnosis, and surveillance: the WHO/ICUD consensus. Urol Int 2015; 94: 1–24.
2.
Sylvester RJ, et al: Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 2006; 49: 466–477; discussion 475–477.
3.
Babjuk M, et al: EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: update 2016. Eur Urol 2017; 71: 447–461.
4.
Simpson AJ, et al: Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 2005; 5: 615–625.
5.
Scanlan MJ, Simpson AJ, Old LJ: The cancer/testis genes: review, standardization, and commentary. Cancer Immun 2004; 4: 1.
6.
Kerkar SP, et al: MAGE-A is more highly expressed than NY-ESO-1 in a systematic immunohistochemical analysis of 3668 cases. J Immunother 2016; 39: 181–187.
7.
Patard JJ, et al: Expression of MAGE genes in transitional-cell carcinomas of the urinary bladder. Int J Cancer 1995; 64: 60–64.
8.
Nishiyama T, et al: Immunotherapy of bladder cancer using autologous dendritic cells pulsed with human lymphocyte antigen-A24-specific MAGE-3 peptide. Clin Cancer Res 2001; 7: 23–31.
9.
Sharma P, et al: Cancer-testis antigens: expression and correlation with survival in human urothelial carcinoma. Clin Cancer Res 2006; 12: 5442–5447.
10.
Picard V, et al: MAGE-A9 mRNA and protein expression in bladder cancer. Int J Cancer 2007; 120: 2170–2177.
11.
Mengus C, et al: MAGE-A10 cancer/testis antigen is highly expressed in high-grade non-muscle-invasive bladder carcinomas. Int J Cancer 2013; 132: 2459–2463.
12.
Dyrskjøt L, et al: Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma. Br J Cancer 2012; 107: 116–122.
13.
Kurashige T, et al: Ny-ESO-1 expression and immunogenicity associated with transitional cell carcinoma: correlation with tumor grade. Cancer Res 2001; 61: 4671–4674.
14.
Makise N, et al: MAGE-A expression, immune microenvironment, and prognosis in upper urinary tract carcinoma. Hum Pathol 2016; 50: 62–69.
15.
Mahoney KM, Atkins MB: Prognostic and predictive markers for the new immunotherapies. Oncology (Williston Park) 2014; 28(suppl 3): 39–48.
16.
Rosenberg SA, Restifo NP: Adoptive cell transfer as personalized immunotherapy for human cancer. Science 2015; 348: 62–68.
© 2018 S. Karger AG, Basel
2018
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