Journal List > Tuberc Respir Dis > v.69(6) > 1001567

TOOLS
Lee, Yun, Lee, Oh, Song, Sohn, Kim, Han, Kim, and Kim: The Clinical Implication of MAGE Gene Detection in Bronchial Washing Fluid in Routine Practice
Original Article
Tuberculosis and Respiratory Diseases

Tuberculosis and Respiratory Diseases 2010; 69(6): 442-449.

Published online: 31 December 2010

DOI: https://doi.org/10.4046/trd.2010.69.6.442

The Clinical Implication of MAGE Gene Detection in Bronchial Washing Fluid in Routine Practice

Seung June Lee, M.D.1, Myung Jae Yun, M.D.1, Seong Tae Lee, M.D.1, Hye Jin Oh, M.D.1, Sook Hee Song, M.D.1, In Sohn, M.D.1, Yeon Jung Kim, M.D.2, Kyung Hoon Han, M.D.2, Sun Hee Kim, M.D.2, Su Hyun Kim, M.D.1

1Department of Internal Medicine, Seoul Medical Center, Seoul, Korea.

2Clinical Research Medical Instutute, Seoul Medical Center, Seoul, Korea.

Address for correspondence: Su Hyun Kim, M.D. Department of Internal Medicine, Seoul Medical Center, 171-1, Samsung 1-dong, Gangnam-gu, Seoul 135-740, Korea. Phone: 82-2-3430-0606, Fax: 82-2-3430-0438, sammy7597@naver.com

Received 22 August 2010       Accepted 12 October 2010

Copyright © 2010. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

Abstract

Background

Melanoma antigen genes (MAGE) are expressed in many human malignant cells and are silent in normal tissues other than in testis and in placenta. But MAGE expression in benign lung diseases, such as pulmonary tuberculosis or cases with severe inflammation, needs further evaluation to overcome false-positive findings. We evaluated detection rates of the melanoma antigen genes (MAGE) RT-nested PCR in bronchoscopic washing samples from patients with benign lung disease, as well as in patients with malignancies.

Methods

Bronchial washing fluid from 122 patients was used for cytological examination and MAGE gene detection using RT-nested-PCR of common A1-6 mRNA. We compared the results from the RT-nested PCR and the pathologic or bacteriologic diagnosis. We also analyzed the expression rate and false positive rate of MAGE gene.

Results

Among 122 subjects, lung cancer was diagnosed in 23 patients and benign lung disease was diagnosed in 99 patients. In patients with lung cancer, the positive rate of MAGE expression was 47.8% (11/23) and in benign lung disease group, the expression rate was 14.1% (14/99). Among benign lung disease group, the expression rate of MAGE gene (25.0%) in patients with pulmonary tuberculosis (11/44) was especially high.

Conclusion

MAGE A1-6 RT-nested PCR of bronchial washing fluid can be used as a complementary method in lung cancer, but that test results in a high false positive rate in tuberculosis patients.

Keywords: Melanoma Antigen Gene, Bronchial Washing Fluid, Tuberculosis, Lung Neoplasms

Figures and Tables

Figure 1
Amplification of MAGE A1-6 genes and GAPDH gene from patients with Anthracotic nodule (1), NTM lung disease (2), Adenocarcinoma (3), Pneumonia, MRSA (4), Aspergilloma (5), Pulmonary TB (6), Benign tumor (7) and BOOP (8). MAGE gene were amplified by RT-nested PCR, and GAPD gene by RT-PCR. M: size marker; P: positive control; N: negative control; MAGE: melanoma antigen genes; GAPDH: glyceraldehydes phosphate dehydrogenase.
trd-69-442-g001
Table 1
Characteristics of patients
trd-69-442-i001
Table 2
Expression rate of MAGE Al-A6 RT-nested PCR in bronchial washing fluid according to histologic types
trd-69-442-i002

MAGE: melanoma antigen genes; RT-nested PCR: reverse transcriptase- nested polymerase chain reaction; NSCLC: non-small cell lung cancer; BALToma: bronchus-associated lymphoid tissue lymphoma.

Table 3
Expression rate of MAGE Al-A6 RT-nested PCR in bronchial washing fluid with benign lung disease
trd-69-442-i003

MAGE: melanoma antigen genes; RT-nested PCR: reverse transcriptase- nested polymerase chain reaction; NTM: non-tuberculous mycobacterium; ILD: interstitial lung disease.

Table 4
Patient characteristics with positive expression of MAGE A1-6 RT-nested PCR within the benign group
trd-69-442-i004

MAGE: melanoma antigen genes; RT-nested PCR: reverse transcriptase-nested polymerase chain reaction; BWF: bronchial washing fluid; EBTB: endobronchial tuberculosis; py: pack-years of cigarette; TDL: tuberculosis-destroyed lung; DM: diabetes mellitus; CVA: cerebrovascular; COPD: chronic obstructive pulmonary disease; HTN: hypertension; MRSA: methicillin resistant staphylococcus aureus.

Table 5
Expression Rate of MAGE and cytologic examinations
trd-69-442-i005

MAGE: melanoma antigen genes.

References

1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009. 59:225–249.
2. Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker S Jr, et al. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol. 2004. 22:330–353.
3. Toyoda Y, Nakayama T, Kusunoki Y, Iso H, Suzuki T. Sensitivity and specificity of lung cancer screening using chest low-dose computed tomography. Br J Cancer. 2008. 98:1602–1607.
4. Jheon S, Hyun DS, Lee SC, Yoon GS, Jeon CH, Park JW, et al. Lung cancer detection by a RT-nested PCR using MAGE A1--6 common primers. Lung Cancer. 2004. 43:29–37.
5. Yook DS, Shin HS, Choi P, Kim JH, Shin SH, Ok CH, et al. Expression of MAGE in the induced sputum of lung cancer patients. Tuberc Respir Dis. 2002. 53:265–274.
6. Jungbluth AA, Busam KJ, Kolb D, Iversen K, Coplan K, Chen YT, et al. Expression of MAGE-antigens in normal tissues and cancer. Int J Cancer. 2000. 85:460–465.
7. Weynants P, Lethé B, Brasseur F, Marchand M, Boon T. Expression of mage genes by non-small-cell lung carcinomas. Int J Cancer. 1994. 56:826–829.
8. Shichijo S, Hayashi A, Takamori S, Tsunosue R, Hoshino T, Sakata M, et al. Detection of MAGE-4 protein in lung cancers. Int J Cancer. 1995. 64:158–165.
9. Gotoh K, Yatabe Y, Sugiura T, Takagi K, Ogawa M, Takahashi T, et al. Frequency of MAGE-3 gene expression in HLA-A2 positive patients with non-small cell lung cancer. Lung Cancer. 1998. 20:117–125.
10. Yoshimatsu T, Yoshino I, Ohgami A, Takenoyama M, Hanagiri T, Nomoto K, et al. Expression of the melanoma antigen-encoding gene in human lung cancer. J Surg Oncol. 1998. 67:126–129.
11. Kim H, Kim SJ, Lee SH, Seong HS, Lee KO, Jeon CH, et al. Usefulness of melanoma antigen (MAGE) gene analysis in tissue samples from percutaneous needle aspiration biopsy of suspected lung cancer lesions. Lung Cancer. 2010. 69:284–288.
12. Kim KC, Seo CG, Park SH, Choi WI, Han SB, Jeon YJ, et al. Diagnostic utility of MAGE expression in exudative pleural effusion. Tuberc Respir Dis. 2004. 56:159–168.
13. Shin KC, Lee SJ, Kim KJ, Lee JW, Kim HJ, Chung JH, et al. The expression of melanoma antigen encoding gene in lung cancer. Korean J Med. 2005. 68:647–655.
14. Kim HR, Kim TH, Chung JH, Yoon HI, Lee CT, Kang CH, et al. The detection of peripheral lung cancer by MAGE A1-6 RT-nested PCR in bronchial washing specimens. Lung Cancer. 2009. 65:166–169.
15. Kim S, Kim H, Kwon OJ, Chung MP, Suh GY, Koh WJ, et al. The utility of MAGE gene detection in bronchial washing fluid for patients with peripheral NSCLC. Tuberc Respir Dis. 2008. 64:15–21.
16. Jung MH, Kim JH, Kim JH, Park KR, Oak CH, Cho HM, et al. Expression of MAGE and GAGE genes in the bronchogenic cancer tissues obtained by bronchoscopy. Korean J Med. 2002. 62:58–68.
17. Park JW, Kwon TK, Kim IH, Sohn SS, Kim YS, Kim CI, et al. A new strategy for the diagnosis of MAGE-expressing cancers. J Immunol Methods. 2002. 266:79–86.
18. Park JK, Jo YS, Jang SJ, Park YS, Choi CM. Clinical benefits of narrow band imaging bronchoscopy in central lung cancer. Tuberc Respir Dis. 2010. 68:16–21.
19. De Smet C, De Backer O, Faraoni I, Lurquin C, Brasseur F, Boon T. The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc Natl Acad Sci USA. 1996. 93:7149–7153.
20. Becker JC, Gillitzer R, Bröcker EB. A member of the melanoma antigen-encoding gene (MAGE) family is expressed in human skin during wound healing. Int J Cancer. 1994. 58:346–348.
21. Jang SJ, Soria JC, Wang L, Hassan KA, Morice RC, Walsh GL, et al. Activation of melanoma antigen tumor antigens occurs early in lung carcinogenesis. Cancer Res. 2001. 61:7959–7963.
22. Liang HY, Li XL, Yu XS, Guan P, Yin ZH, He QC, et al. Facts and fiction of the relationship between preexisting tuberculosis and lung cancer risk: a systematic review. Int J Cancer. 2009. 125:2936–2944.
23. Engels EA, Shen M, Chapman RS, Pfeiffer RM, Yu YY, He X, et al. Tuberculosis and subsequent risk of lung cancer in Xuanwei, China. Int J Cancer. 2009. 124:1183–1187.
24. Mecklenburg I, Stratakis DF, Huber RM, Häussinger K, Morresi-Hauf A, Riethmüller G, et al. Detection of melanoma antigen-A expression in sputum and bronchial lavage fluid of patients with lung cancer. Chest. 2004. 125:164S–166S.
TOOLS
Similar articles