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Published in: International Journal of Clinical Oncology 5/2016

01-10-2016 | Original Article

MAGE-A1–6   expression in patients with head and neck squamous cell carcinoma: impact on clinical patterns and oncologic outcomes

Authors: Sang Tae Noh, Hyoung Shin Lee, Soo Jin Lim, Sung Won Kim, Hee Kyung Chang, Junghwan Oh, Chang-Ho Jeon, Jong Wook Park, Kang Dae Lee

Published in: International Journal of Clinical Oncology | Issue 5/2016

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Abstract

Background

Various subtypes of melanoma-associated antigens (MAGEs) are expressed in the tumor tissues of patients with head and neck squamous cell carcinoma (HNSCC). However, little data are currently available on how the gene expression of MAGEs impacts clinical patterns and oncologic outcomes. We have therefore evaluated the expression of MAGE-A1–6 (A1–6) subtypes in tumor tissues of patients with HNSCC and the clinical impact of this expression.

Methods

This was a retrospective review of 53 patients with histologically proven HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx who underwent both treatment and analysis by reverse transcription (RT)-PCR assay with a common primer to identify the expression of MAGE-A1–6 subtypes in the tumor tissue. The clinicopathologic factors and oncologic outcomes of these patients and the correlations of both to MAGE-A1–6 gene expression were analyzed.

Results

MAGE-A1–6 subtypes were expressed in the tumor tissues of 37 patients (69.8 %). Patient age of ≥65 years [p = 0.031, hazard ratio (HR) 4.866] and advanced American Joint Committee on Cancer stage (p = 0.035, HR 4.291) were independent risk factors for expression of MAGE-A1–6 subtypes. Patients with MAGE-A1–6 expression had lower disease-free survival (p = 0.029), disease-specific survival (p = 0.070), and overall survival (p = 0.017) rates. Overall survival rate was independently associated to chemotherapy (p = 0.011, HR 2.859), while no surgery (p = 0.050, HR 2.400) and MAGE-A1–6 expression (p = 0.050, HR 2.527) showed borderline significance.

Conclusion

In our patient group the expression of MAGE-A1–6 subtypes in tumor tissues of patients with HNSCC was correlated with advanced clinical stage of cancer and poor oncologic outcomes. We suggest that gene expression of MAGE-A1–6 subtypes may be considered to be a predictive factor to determine patient treatment or follow-up strategy.
Literature
3.
4.
go back to reference Figueiredo DL, Mamede RC, Proto-Siqueira R et al (2006) Expression of cancer testis antigens in head and neck squamous cell carcinomas. Head Neck 28:614–619CrossRefPubMed Figueiredo DL, Mamede RC, Proto-Siqueira R et al (2006) Expression of cancer testis antigens in head and neck squamous cell carcinomas. Head Neck 28:614–619CrossRefPubMed
5.
go back to reference Simpson AJ, Caballero OL, Jungbluth A et al (2005) Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5:615–625CrossRefPubMed Simpson AJ, Caballero OL, Jungbluth A et al (2005) Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5:615–625CrossRefPubMed
6.
7.
go back to reference Sang M, Wang L, Ding C et al (2011) Melanoma-associated antigen genes—an update. Cancer Lett 302:85–90CrossRefPubMed Sang M, Wang L, Ding C et al (2011) Melanoma-associated antigen genes—an update. Cancer Lett 302:85–90CrossRefPubMed
8.
go back to reference Lian Y, Sang M, Ding C et al (2012) Expressions of MAGE-A10 and MAGE-A11 in breast cancers and their prognostic significance: a retrospective clinical study. J Cancer Res Clin Oncol 138:519–527CrossRefPubMed Lian Y, Sang M, Ding C et al (2012) Expressions of MAGE-A10 and MAGE-A11 in breast cancers and their prognostic significance: a retrospective clinical study. J Cancer Res Clin Oncol 138:519–527CrossRefPubMed
9.
go back to reference Rogner UC, Wilke K, Steck E et al (1995) The melanoma antigen gene (MAGE) family is clustered in the chromosomal band Xq28. Genomics 29:725–731CrossRefPubMed Rogner UC, Wilke K, Steck E et al (1995) The melanoma antigen gene (MAGE) family is clustered in the chromosomal band Xq28. Genomics 29:725–731CrossRefPubMed
10.
go back to reference Song DW, Shin SJ, Kim DE et al (2008) Detection of MAGE and SSX gene expressions by RT-nested PCR using common primers in head and neck cancer. Clin Exp Otorhinolaryngol 1:97CrossRefPubMedPubMedCentral Song DW, Shin SJ, Kim DE et al (2008) Detection of MAGE and SSX gene expressions by RT-nested PCR using common primers in head and neck cancer. Clin Exp Otorhinolaryngol 1:97CrossRefPubMedPubMedCentral
11.
go back to reference Lee KD, Lee HS, Kim SW et al (2015) Clinical significance of melanoma-associated antigen A1–6 expression in sputum of patients with squamous cell carcinoma of the larynx and hypopharynx. Head Neck 38[Suppl 1]:E736-40 Lee KD, Lee HS, Kim SW et al (2015) Clinical significance of melanoma-associated antigen A1–6 expression in sputum of patients with squamous cell carcinoma of the larynx and hypopharynx. Head Neck 38[Suppl 1]:E736-40
12.
go back to reference Cuffel C, Rivals J-P, Zaugg Y et al (2011) Pattern and clinical significance of cancer-testis gene expression in head and neck squamous cell carcinoma. Int J Cancer 128:2625–2634CrossRefPubMed Cuffel C, Rivals J-P, Zaugg Y et al (2011) Pattern and clinical significance of cancer-testis gene expression in head and neck squamous cell carcinoma. Int J Cancer 128:2625–2634CrossRefPubMed
13.
go back to reference Pastorcic-Grgic M, Sarcevic B, Dosen D et al (2010) Prognostic value of MAGE-A and NY-ESO-1 expression in pharyngeal cancer. Head Neck 32:1178–1184CrossRefPubMed Pastorcic-Grgic M, Sarcevic B, Dosen D et al (2010) Prognostic value of MAGE-A and NY-ESO-1 expression in pharyngeal cancer. Head Neck 32:1178–1184CrossRefPubMed
14.
go back to reference Montoro JR, Mamede RC, Neder Serafini L et al (2012) Expression of cancer-testis antigens MAGE-A4 and MAGE-C1 in oral squamous cell carcinoma. Head Neck 34:1123–1128CrossRefPubMed Montoro JR, Mamede RC, Neder Serafini L et al (2012) Expression of cancer-testis antigens MAGE-A4 and MAGE-C1 in oral squamous cell carcinoma. Head Neck 34:1123–1128CrossRefPubMed
15.
go back to reference Park MS, Park JW, Jeon CH et al (2002) Expression of melanoma antigen-encoding genes (MAGE) by common primers for MAGE-A1 to -A6 in colorectal carcinomas among Koreans. J Korean Med Sci 17:497–501CrossRefPubMedPubMedCentral Park MS, Park JW, Jeon CH et al (2002) Expression of melanoma antigen-encoding genes (MAGE) by common primers for MAGE-A1 to -A6 in colorectal carcinomas among Koreans. J Korean Med Sci 17:497–501CrossRefPubMedPubMedCentral
16.
go back to reference Kim HR, Kim TH, Chung JH et al (2009) The detection of peripheral lung cancer by MAGE A1–6 RT-nested PCR in bronchial washing specimens. Lung Cancer 65:166–169CrossRefPubMed Kim HR, Kim TH, Chung JH et al (2009) The detection of peripheral lung cancer by MAGE A1–6 RT-nested PCR in bronchial washing specimens. Lung Cancer 65:166–169CrossRefPubMed
17.
go back to reference Lee HS, Kim SW, Hong JC et al (2013) Expression of MAGE A1–6 and the clinical characteristics of papillary thyroid carcinoma. Anticancer Res 33:1731–1735PubMed Lee HS, Kim SW, Hong JC et al (2013) Expression of MAGE A1–6 and the clinical characteristics of papillary thyroid carcinoma. Anticancer Res 33:1731–1735PubMed
18.
go back to reference Jheon S, Hyun DS, Lee SC et al (2004) Lung cancer detection by a RT-nested PCR using MAGE A1–6 common primers. Lung Cancer 43:29–37CrossRefPubMed Jheon S, Hyun DS, Lee SC et al (2004) Lung cancer detection by a RT-nested PCR using MAGE A1–6 common primers. Lung Cancer 43:29–37CrossRefPubMed
19.
go back to reference Jeon CH, Kim DD, Lee HI et al (2011) Melanoma-associated antigen (MAGE) expression in the normal mucosa around colorectal cancer after curative resection: presence of undetectable free cancer cells. Int J Biol Markers 26:88–93CrossRefPubMed Jeon CH, Kim DD, Lee HI et al (2011) Melanoma-associated antigen (MAGE) expression in the normal mucosa around colorectal cancer after curative resection: presence of undetectable free cancer cells. Int J Biol Markers 26:88–93CrossRefPubMed
20.
go back to reference Park JW, Kwon TK, Kim IH et al (2002) A new strategy for the diagnosis of MAGE-expressing cancers. J Immunol Methods 266:79–86CrossRefPubMed Park JW, Kwon TK, Kim IH et al (2002) A new strategy for the diagnosis of MAGE-expressing cancers. J Immunol Methods 266:79–86CrossRefPubMed
21.
go back to reference Jang SJ, Soria JC, Wang L et al (2001) Activation of melanoma antigen tumor antigens occurs early in lung carcinogenesis. Cancer Res 61:7959–7963PubMed Jang SJ, Soria JC, Wang L et al (2001) Activation of melanoma antigen tumor antigens occurs early in lung carcinogenesis. Cancer Res 61:7959–7963PubMed
22.
go back to reference Ogata K, Aihara R, Mochiki E et al (2011) Clinical significance of melanoma antigen-encoding gene-1 (MAGE-1) expression and its correlation with poor prognosis in differentiated advanced gastric cancer. Ann Surg Oncol 18:1195–1203CrossRefPubMed Ogata K, Aihara R, Mochiki E et al (2011) Clinical significance of melanoma antigen-encoding gene-1 (MAGE-1) expression and its correlation with poor prognosis in differentiated advanced gastric cancer. Ann Surg Oncol 18:1195–1203CrossRefPubMed
23.
go back to reference Yamashita N, Ishibashi H, Hayashida K et al (1996) High frequency of the MAGE-1 gene expression in hepatocellular carcinoma. Hepatology 24:1437–1440PubMed Yamashita N, Ishibashi H, Hayashida K et al (1996) High frequency of the MAGE-1 gene expression in hepatocellular carcinoma. Hepatology 24:1437–1440PubMed
24.
go back to reference Kocher T, Zheng M, Bolli M et al (2002) Prognostic relevance of MAGE-A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: a tissue microarray study. Int J Cancer 100:702–705CrossRefPubMed Kocher T, Zheng M, Bolli M et al (2002) Prognostic relevance of MAGE-A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: a tissue microarray study. Int J Cancer 100:702–705CrossRefPubMed
25.
go back to reference Monte M, Simonatto M, Peche LY et al (2006) MAGE-A tumor antigens target p53 transactivation function through histone deacetylase recruitment and confer resistance to chemotherapeutic agents. Proc Natl Acad Sci USA103:11160–11165CrossRefPubMedPubMedCentral Monte M, Simonatto M, Peche LY et al (2006) MAGE-A tumor antigens target p53 transactivation function through histone deacetylase recruitment and confer resistance to chemotherapeutic agents. Proc Natl Acad Sci USA103:11160–11165CrossRefPubMedPubMedCentral
26.
go back to reference Yang B, O’Herrin SM, Wu J et al (2007) MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines. Cancer Res 67:9954–9962CrossRefPubMed Yang B, O’Herrin SM, Wu J et al (2007) MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines. Cancer Res 67:9954–9962CrossRefPubMed
28.
go back to reference Pereira CM, Gomes CC, De Fatima Correia Silva J et al (2012) Evaluation of MAGE A1 in oral squamous cell carcinoma. Oncol Rep 27:1843–1848PubMed Pereira CM, Gomes CC, De Fatima Correia Silva J et al (2012) Evaluation of MAGE A1 in oral squamous cell carcinoma. Oncol Rep 27:1843–1848PubMed
29.
go back to reference Ries J, Vairaktaris E, Mollaoglu N et al (2008) Expression of melanoma-associated antigens in oral squamous cell carcinoma. J Oral Pathol Med 37:88–93CrossRefPubMed Ries J, Vairaktaris E, Mollaoglu N et al (2008) Expression of melanoma-associated antigens in oral squamous cell carcinoma. J Oral Pathol Med 37:88–93CrossRefPubMed
30.
go back to reference De Plaen E, Arden K, Traversari C et al (1994) Structure, chromosomal localization, and expression of 12 genes of the MAGE family. Immunogenetics 40:360–369CrossRefPubMed De Plaen E, Arden K, Traversari C et al (1994) Structure, chromosomal localization, and expression of 12 genes of the MAGE family. Immunogenetics 40:360–369CrossRefPubMed
31.
go back to reference Dhodapkar MV, Osman K, Teruya-Feldstein J et al (2003) Expression of cancer/testis (CT) antigens MAGE-A1, MAGE-A3, MAGE-A4, CT-7, and NY-ESO-1 in malignant gammopathies is heterogeneous and correlates with site, stage and risk status of disease. Cancer Immun 3:9PubMed Dhodapkar MV, Osman K, Teruya-Feldstein J et al (2003) Expression of cancer/testis (CT) antigens MAGE-A1, MAGE-A3, MAGE-A4, CT-7, and NY-ESO-1 in malignant gammopathies is heterogeneous and correlates with site, stage and risk status of disease. Cancer Immun 3:9PubMed
32.
go back to reference Ries J, Agaimy A, Vairaktaris E et al (2012) Detection of MAGE-A expression predicts malignant transformation of oral leukoplakia. Cancer Invest 30:495–502CrossRefPubMed Ries J, Agaimy A, Vairaktaris E et al (2012) Detection of MAGE-A expression predicts malignant transformation of oral leukoplakia. Cancer Invest 30:495–502CrossRefPubMed
34.
go back to reference Han L, Jiang B, Wu H et al (2014) Expression and prognostic value of MAGE-A9 in laryngeal squamous cell carcinoma. Int J Clin Exp Pathol 7:6734–6742PubMedPubMedCentral Han L, Jiang B, Wu H et al (2014) Expression and prognostic value of MAGE-A9 in laryngeal squamous cell carcinoma. Int J Clin Exp Pathol 7:6734–6742PubMedPubMedCentral
35.
go back to reference Mollaoglu N, Metzler P, Zenk J et al (2011) Prediction of recurrence using exfoliative cytology and melanoma-associated antigen-A mRNA analysis following wide excision of oral squamous cell carcinoma: short report. Cytopathology 22:387–391CrossRefPubMed Mollaoglu N, Metzler P, Zenk J et al (2011) Prediction of recurrence using exfoliative cytology and melanoma-associated antigen-A mRNA analysis following wide excision of oral squamous cell carcinoma: short report. Cytopathology 22:387–391CrossRefPubMed
36.
go back to reference Eura M, Ogi K, Chikamatsu K et al (1995) Expression of the MAGE gene family in human head-and-neck squamous-cell carcinomas. Int J Cancer 64:304–308CrossRefPubMed Eura M, Ogi K, Chikamatsu K et al (1995) Expression of the MAGE gene family in human head-and-neck squamous-cell carcinomas. Int J Cancer 64:304–308CrossRefPubMed
37.
go back to reference Muller-Richter UD, Dowejko A, Driemel O et al (2010) Impact of MAGE-A antigens on taxane response in oral squamous cell carcinoma. Oncol Lett 1:181–185PubMedPubMedCentral Muller-Richter UD, Dowejko A, Driemel O et al (2010) Impact of MAGE-A antigens on taxane response in oral squamous cell carcinoma. Oncol Lett 1:181–185PubMedPubMedCentral
38.
go back to reference Hartmann S, Kriegebaum U, Kuchler N et al (2014) Correlation of MAGE-A tumor antigens and the efficacy of various chemotherapeutic agents in head and neck carcinoma cells. Clin Oral Investig 18:189–197CrossRefPubMed Hartmann S, Kriegebaum U, Kuchler N et al (2014) Correlation of MAGE-A tumor antigens and the efficacy of various chemotherapeutic agents in head and neck carcinoma cells. Clin Oral Investig 18:189–197CrossRefPubMed
39.
go back to reference Hartmann S, Meyer TJ, Brands RC et al (2015) MAGE-A expression clusters and antineoplastic treatment in head and neck cancer. Int J Mol Med 35:1675–1682PubMed Hartmann S, Meyer TJ, Brands RC et al (2015) MAGE-A expression clusters and antineoplastic treatment in head and neck cancer. Int J Mol Med 35:1675–1682PubMed
40.
go back to reference Atanackovic D, Blum I, Cao Y et al (2006) Expression of cancer-testis antigens as possible targets for antigen-specific immunotherapy in head and neck squamous cell carcinoma. Cancer Biol Ther 5:1218–1225CrossRefPubMed Atanackovic D, Blum I, Cao Y et al (2006) Expression of cancer-testis antigens as possible targets for antigen-specific immunotherapy in head and neck squamous cell carcinoma. Cancer Biol Ther 5:1218–1225CrossRefPubMed
Metadata
Title
MAGE-A1–6   expression in patients with head and neck squamous cell carcinoma: impact on clinical patterns and oncologic outcomes
Authors
Sang Tae Noh
Hyoung Shin Lee
Soo Jin Lim
Sung Won Kim
Hee Kyung Chang
Junghwan Oh
Chang-Ho Jeon
Jong Wook Park
Kang Dae Lee
Publication date
01-10-2016
Publisher
Springer Japan
Published in
International Journal of Clinical Oncology / Issue 5/2016
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-016-0989-6

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