MAGE-A is more highly expressed than NY-ESO-1 in a systematic immunohistochemical analysis of 3668 cases

Sid P. Kerkar, Zeng Feng Wang, Jerzy Lasota, Tristen Park, Krishna Patel, Eric Groh, Steven A. Rosenberg, Markku M. Miettinen

Research output: Contribution to journalArticle

Abstract

Two cancer testis antigens, the New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and the melanoma-antigen family A (MAGE-A), represent promising immunotherapy targets due to the low expression of these antigens in nonmalignant tissue. To assess overexpression patterns in various cancers, we performed a systematic immunohistochemical analysis for NYESO- 1 and MAGE-A on tissue array samples of 3668 common epithelial carcinomas (CA) and germ cell tumors of high prevalence and mortality. Here, we find significantly higher expression of MAGE-A (> 50% on tumor cells) compared with NY-ESO-1 in several CAs including cutaneous squamous cell carcinomas (SCC) (52.8%/2.8%), esophageal SCC (50%/0%), head and neck SCC (41.1%/> 1%), bladder urothelial CA (40.4%/8.3%), cervical/anal SCC (37.5%/0%), lung SCC (34%/3.8%), lung adenocarcinomas (27.6%/3.9%), ovarian CA (26.4%/3.6%), endometrial CA (26.3%/1.3%), lung small cell CA (24.4%/2.4%), gastric adenocarcinomas (20%/4%), breast mucinous CA (19.3%/0%), hepatocellular CA (18.8%/1.2%), breast infiltrating ductal CA (16.4%/1.8%), colorectal adenocarcinomas (10.7%/<1%), cholangiocarcinomas (9.8%/0%), thymic CA (9%/4.5%), and mesotheliomas (7.9%/<1%). Furthermore, high expression of MAGEA, but not NY-ESO-1, was seen in whole slide evaluations of an independent cohort of metastatic SCC (45.5%/3.6%) and metastatic CA (13.5%/0%) of various primaries with significantly higher expression of MAGE-A in metastatic SCC compared with other metastatic CA. MAGE-A is also more highly expressed in germ cell tumors, seminomas (69%/3.5%) and nonseminomas (40.1%/4.7%). In summary, MAGE-A is more highly expressed than NY-ESO-1 in a majority of human malignancies, and targeting MAGE-A may benefit a large number of patients.

Original languageEnglish (US)
Pages (from-to)181-187
Number of pages7
JournalJournal of Immunotherapy
Volume39
Issue number4
DOIs
StatePublished - 2016
Externally publishedYes

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Melanoma-Specific Antigens
Squamous Cell Carcinoma
Carcinoma
Germ Cell and Embryonal Neoplasms
Adenocarcinoma
Carcinoma, Ductal, Breast
Antigens
Mucinous Adenocarcinoma
Neoplasms
Seminoma
Thymoma
Cholangiocarcinoma
Mesothelioma
Small Cell Lung Carcinoma
Testicular Neoplasms
Endometrial Neoplasms
Esophageal Squamous Cell Carcinoma
Immunotherapy
Hepatocellular Carcinoma
Stomach

Keywords

  • Cancer
  • Cancer-testis antigens
  • Immuneescape
  • Immunohistochemistry
  • Immunotherapy
  • MAGE-A
  • NYESO
  • Predictive-markers
  • Prognostic-markers
  • Tissue-arrays

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cancer Research
  • Pharmacology

Cite this

Kerkar, S. P., Wang, Z. F., Lasota, J., Park, T., Patel, K., Groh, E., ... Miettinen, M. M. (2016). MAGE-A is more highly expressed than NY-ESO-1 in a systematic immunohistochemical analysis of 3668 cases. Journal of Immunotherapy, 39(4), 181-187. https://doi.org/10.1097/CJI.0000000000000119

MAGE-A is more highly expressed than NY-ESO-1 in a systematic immunohistochemical analysis of 3668 cases. / Kerkar, Sid P.; Wang, Zeng Feng; Lasota, Jerzy; Park, Tristen; Patel, Krishna; Groh, Eric; Rosenberg, Steven A.; Miettinen, Markku M.

In: Journal of Immunotherapy, Vol. 39, No. 4, 2016, p. 181-187.

Research output: Contribution to journalArticle

Kerkar, SP, Wang, ZF, Lasota, J, Park, T, Patel, K, Groh, E, Rosenberg, SA & Miettinen, MM 2016, 'MAGE-A is more highly expressed than NY-ESO-1 in a systematic immunohistochemical analysis of 3668 cases', Journal of Immunotherapy, vol. 39, no. 4, pp. 181-187. https://doi.org/10.1097/CJI.0000000000000119
Kerkar, Sid P. ; Wang, Zeng Feng ; Lasota, Jerzy ; Park, Tristen ; Patel, Krishna ; Groh, Eric ; Rosenberg, Steven A. ; Miettinen, Markku M. / MAGE-A is more highly expressed than NY-ESO-1 in a systematic immunohistochemical analysis of 3668 cases. In: Journal of Immunotherapy. 2016 ; Vol. 39, No. 4. pp. 181-187.
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abstract = "Two cancer testis antigens, the New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and the melanoma-antigen family A (MAGE-A), represent promising immunotherapy targets due to the low expression of these antigens in nonmalignant tissue. To assess overexpression patterns in various cancers, we performed a systematic immunohistochemical analysis for NYESO- 1 and MAGE-A on tissue array samples of 3668 common epithelial carcinomas (CA) and germ cell tumors of high prevalence and mortality. Here, we find significantly higher expression of MAGE-A (> 50{\%} on tumor cells) compared with NY-ESO-1 in several CAs including cutaneous squamous cell carcinomas (SCC) (52.8{\%}/2.8{\%}), esophageal SCC (50{\%}/0{\%}), head and neck SCC (41.1{\%}/> 1{\%}), bladder urothelial CA (40.4{\%}/8.3{\%}), cervical/anal SCC (37.5{\%}/0{\%}), lung SCC (34{\%}/3.8{\%}), lung adenocarcinomas (27.6{\%}/3.9{\%}), ovarian CA (26.4{\%}/3.6{\%}), endometrial CA (26.3{\%}/1.3{\%}), lung small cell CA (24.4{\%}/2.4{\%}), gastric adenocarcinomas (20{\%}/4{\%}), breast mucinous CA (19.3{\%}/0{\%}), hepatocellular CA (18.8{\%}/1.2{\%}), breast infiltrating ductal CA (16.4{\%}/1.8{\%}), colorectal adenocarcinomas (10.7{\%}/<1{\%}), cholangiocarcinomas (9.8{\%}/0{\%}), thymic CA (9{\%}/4.5{\%}), and mesotheliomas (7.9{\%}/<1{\%}). Furthermore, high expression of MAGEA, but not NY-ESO-1, was seen in whole slide evaluations of an independent cohort of metastatic SCC (45.5{\%}/3.6{\%}) and metastatic CA (13.5{\%}/0{\%}) of various primaries with significantly higher expression of MAGE-A in metastatic SCC compared with other metastatic CA. MAGE-A is also more highly expressed in germ cell tumors, seminomas (69{\%}/3.5{\%}) and nonseminomas (40.1{\%}/4.7{\%}). In summary, MAGE-A is more highly expressed than NY-ESO-1 in a majority of human malignancies, and targeting MAGE-A may benefit a large number of patients.",
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AU - Wang, Zeng Feng

AU - Lasota, Jerzy

AU - Park, Tristen

AU - Patel, Krishna

AU - Groh, Eric

AU - Rosenberg, Steven A.

AU - Miettinen, Markku M.

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N2 - Two cancer testis antigens, the New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and the melanoma-antigen family A (MAGE-A), represent promising immunotherapy targets due to the low expression of these antigens in nonmalignant tissue. To assess overexpression patterns in various cancers, we performed a systematic immunohistochemical analysis for NYESO- 1 and MAGE-A on tissue array samples of 3668 common epithelial carcinomas (CA) and germ cell tumors of high prevalence and mortality. Here, we find significantly higher expression of MAGE-A (> 50% on tumor cells) compared with NY-ESO-1 in several CAs including cutaneous squamous cell carcinomas (SCC) (52.8%/2.8%), esophageal SCC (50%/0%), head and neck SCC (41.1%/> 1%), bladder urothelial CA (40.4%/8.3%), cervical/anal SCC (37.5%/0%), lung SCC (34%/3.8%), lung adenocarcinomas (27.6%/3.9%), ovarian CA (26.4%/3.6%), endometrial CA (26.3%/1.3%), lung small cell CA (24.4%/2.4%), gastric adenocarcinomas (20%/4%), breast mucinous CA (19.3%/0%), hepatocellular CA (18.8%/1.2%), breast infiltrating ductal CA (16.4%/1.8%), colorectal adenocarcinomas (10.7%/<1%), cholangiocarcinomas (9.8%/0%), thymic CA (9%/4.5%), and mesotheliomas (7.9%/<1%). Furthermore, high expression of MAGEA, but not NY-ESO-1, was seen in whole slide evaluations of an independent cohort of metastatic SCC (45.5%/3.6%) and metastatic CA (13.5%/0%) of various primaries with significantly higher expression of MAGE-A in metastatic SCC compared with other metastatic CA. MAGE-A is also more highly expressed in germ cell tumors, seminomas (69%/3.5%) and nonseminomas (40.1%/4.7%). In summary, MAGE-A is more highly expressed than NY-ESO-1 in a majority of human malignancies, and targeting MAGE-A may benefit a large number of patients.

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