Journal List > Korean J Urol > v.50(8) > 1005383

Gi, Kim, Seo, Jeon, and Lee: Comparison of the Urinary Melanoma Antigen Gene Expression (MAGE) Test and Urinary Cytology for Bladder Cancer Screening

Abstract

Purpose

In bladder cancer screening, many methods such as urinary cytology, bladder tumor antigen, and nuclear matrix protein-22 are well known. To learn the value of urinary melanoma antigen gene expression (MAGE) in bladder cancer screening, we compared the urinary MAGE test with irrigated urinary cytology.

Materials and Methods

From July 2000 to July 2007, a total of 142 patients were enrolled in this study. We divided these patients into 2 groups. Eighty-eight patients with bladder cancer were included in group I. Group II consisted of 54 patients who had been treated for bladder cancer and had no evidence of tumor by cystoscopy and irrigated urinary cytology. Urinary cytology, urinary MAGE test, and cystoscopy were performed in all patients. The urinary MAGE test was done by reverse transcriptase polymerase chain reaction (RT-PCR). Sensitivity and specificity were investigated according to cancer grade and stage.

Results

The overall sensitivity of the urinary MAGE test and urinary cytology was 69.3% (61/88) and 53.4% (47/88), respectively (p=0.03). The specificity of the urinary MAGE test and urinary cytology was 75.9% (41/54) and 83.3% (45/54), respectively (p=0.34). The sensitivity of each test in superficial tumors (Ta, T1) was 65.5% (38/58) and 46.6% (27/58), respectively (p=0.04). In advanced disease (≥T2), the sensitivity of the tests was 76.7% (23/30) and 66.7% (20/30), respectively (p=0.39). The sensitivity of the urinary MAGE test in grade 1 tumors (60.5%, 23/38) was significantly higher (p=0.01) than that of urinary cytology (31.6%, 12/38).

Conclusions

The urinary MAGE test was more sensitive than urinary cytology in bladder cancer screening. We consider the urinary MAGE test to possibly be a valuable test together with urinary cytology, especially for Grade 1 and Ta, T1 bladder cancer.

REFERENCES

1. Raghavan D, Shipley WU, Garnick MB, Russell PJ, Richie JP. Biology and management of bladder cancer. N Engl J Med. 1990; 322:1129–38.
crossref
2. Loening S, Narayana A, Yoder L, Slymen D, Weinstein S, Penick G, et al. Factors influencing the recurrence rate of bladder cancer. J Urol. 1980; 123:29–31.
crossref
3. Murphy WM, Emerson LD, Chandler RW, Moinuddin SM, Soloway MS. Flow cytometry versus urinary cytology in the evaluation of patients with bladder cancer. J Urol. 1986; 136:815–9.
crossref
4. Murphy WM, Soloway MS, Jukkola AF, Carbtree WN, Ford KS. Urinary cytology and bladder cancer. The cellular features of transitional cell neoplasms. Cancer. 1984; 53:1555–65.
crossref
5. Lokeshwar VB, Soloway MS. Current bladder tumor tests: Does their projected utility fulfill clinical necessity? J Urol. 2001; 165:1067–77.
crossref
6. Sharma S, Zippe CD, Pandrangi L, Nelson D, Agarwal A. Exclusion criteria enhance the specificity and positive predictive value of NMP22 and BTA stat. J Urol. 1999; 162:53–7.
7. Kwon DH, Hong SJ. The clinical utility of BTA TRAK, BTA stat, NMP22 and urine cytology in the diagnosis of bladder cancer: a comparative study. Korean J Urol. 2003; 44:721–6.
8. Kim SR, Ahn MW, Kim YB, Lim YA, Kim SJ. Comparison of BTA TRAK assay with voided urine cytology in the detection of primary and recurrent bladder cancer. Korean J Urol. 2002; 43:296–302.
9. Kinders R, Jones T, Root R, Bruce C, Murchison H, Corey M, et al. Complement factor H or a related protein is a marker for transitional cell cancer of the bladder. Clin Cancer Res. 1998; 4:2511–20.
10. Ianari A, Sternberg CN, Rossetti A, Van Rijn A, Deidda A, Giannarelli D, et al. Results of Bard BTA test in monitoring patients with a history of transitional cell cancer of the bladder. Urology. 1997; 49:786–9.
crossref
11. Zeitlin S, Parent A, Silverstein S, Efstratiadis A. Pre-mRNA splicing and the nuclear matrix. Mol Cell Biol. 1987; 7:111–20.
crossref
12. Lotan Y, Elias K, Svatek RS, Bagrodia A, Nuss G, Moran B, et al. Bladder cancer screening in a high risk asymptomatic population using a point of care urine based protein tumor marker. J Urol. 2009; 182:52–7.
crossref
13. Sarosdy MF, Hudson MA, Ellis WJ, Soloway MS, deVere White R, Sheinfeld J, et al. Improved detection of recurrent bladder cancer using the Bard BTA stat test. Urology. 1997; 50:349–53.
crossref
14. Kim JS, Lee HM, Lee KH. Comparison of the Bard BTA stat test, Bard BTA test, NMP-22 test and cytology in the diagnosis of bladder cancer. Korean J Urol. 2000; 41:833–7.
15. van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991; 254:1643–7.
crossref
16. De Plaen E, Arden K, Traversari C, Gaforio JJ, Szikora JP, De Smet C, et al. Structure, chromosomal localization, and expression of 12 genes of the MAGE family. Immunogenetics. 1994; 40:360–9.
crossref
17. Lucas S, Brasseur F, Boon T. A new MAGE gene with ubiquitous expression does not code for known MAGE antigens recognized by T cells. Cancer Res. 1999; 59:4100–3.
18. Barker PA, Salehi A. The MAGE proteins: emerging roles in cell cycle progression, apoptosis, and neurogenetic disease. J Neurosci Res. 2002; 67:705–12.
crossref
19. Kim YM, Lee YH, Shin SH, Kim EH, Choi YW, Lee KM, et al. Expression of MAGE-1,-2, and -3 genes in gastric carcinomas and cancer cell lines derived from Korean patients. J Korean Med Sci. 2001; 16:62–8.
20. Li J, Yang Y, Fujie T, Tanaka F, Mimori K, Haraguchi M, et al. Expression of the MAGE gene family in human gastric carcinoma. Anticancer Res. 1997; 17:3559–63.
21. Mori M, Inoue H, Mimori K, Shibuta K, Baba K, Nakashima H, et al. Expression of MAGE genes in human colorectal carcinoma. Ann Surg. 1996; 224:183–8.
crossref
22. Weynants P, Lethe B, Brasseur F, Marchand M, Boon T. Expression of MAGE genes by non-small-cell lung carcinomas. Int J Cancer. 1994; 56:826–9.
crossref
23. Russo M, Traversari C, Verrecchia A, Mottolese M, Natali PG, Bordignon C. Expression of MAGE gene family in primary and metastatic human breast cancer: implications for tumor antigen-specific immunotherapy. Int J Cancer. 1995; 64:216–21.
24. Yamashita N, Ishibashi H, Hayashida K, Kudo J, Takenaka K, Itoh K, et al. High frequency of the MAGE-1 gene expression in hepatocellular carcinoma. Hepatology. 1996; 24:1437–40.
crossref
25. Russo V, Dalerba P, Ricci A, Bonazzi C, Leone BE, Mangioni C, et al. MAGE BAGE, and GAGE genes expression in fresh epithelial ovarian carcinomas. Int J Cancer. 1996; 67:457–60.
26. Shichijo S, Tsunosue R, Masuoka K, Natori H, Tamai M, Miyajima J, et al. Expression of the MAGE gene family in human lymphocytic leukemia. Cancer Immunol Immunother. 1995; 41:90–103.
crossref
27. Patard JJ, Barsseur F, Gil-Diez S, Radvanyi F, Marchand M, Francois P, et al. Expression of MAGE genes in transitional-cell carcinomas of the urinary bladder. Int J Cancer. 1995; 64:60–4.
28. Bar-Haim E, Paz A, Machlenkin A, Hazzan D, Tirosh B, Carmon L, et al. MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides. Br J Cancer. 2004; 91:398–407.
crossref
29. Kim DY, Cho HJ, Oh HK, Shin IH, Jeon CH. Comparison of the urine ThinPrep test and melanoma antigen gene RT-PCR for the detection of bladder cancer according to three urine collection methods. Korean J Lab Med. 2007; 27:50–5.
crossref

Table 1.
Primer sequences used for melanoma antigen gene A1-6 reverse transcriptase (RT)-nested polymerase chain reaction (PCR)
Primers Usage Sequence Size
C1 Outer sense 5′-CTG AAG GAG AAG ATC TGC C-3′ 850 bp
C2 Outer antisense 5′-CTC CAG GTA GTT TTC CTG CAC-3′
C3 Inner sense 5′-CTG AAG GAG AAG ATC TGC CAG TG-3′ 490 bp
C4 Inner antisense 5′-CCA GCA TTT CTG CCT TTG TGA-3′
Table 2.
Comparison of overall sensitivity and specificity of urinary cytology and the MAGE test
  MAGE (%) Cytology (%) p-value
Sensitivity 61/88 (69.3) 47/88 (53.4) 0.03
Specificity 41/54 (75.9) 45/54 (83.3) 0.34

MAGE: melanoma antigen gene

Table 3.
Comparison of the sensitivity of urinary cytology and the MAGE test according to stage
Stage MAGE (%) Cytology (%) p-value
Ta, T1 38/58 (65.5) 27/58 (46.6) 0.04
≥T2 23/30 (76.7) 20/30 (66.7) 0.39

MAGE: melanoma antigen gene

Table 4.
Comparison of the sensitivity of urinary cytology and thMAGE test according to grade
Grade MAGE (%) Cytology (%) p-value
I 23/38 (60.5) 12/38 (31.6) 0.01
II 20/30 (66.7) 19/30 (63.3) 0.28
III 18/20 (90.0) 16/20 (80.0) 0.66

MAGE: melanoma antigen gene

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