MAGE-A is More Highly Expressed Than NY-ESO-1 in a Systematic Immunohistochemical Analysis of 3668 Cases

Our plain-English summary of MAGE-A is More Highly Expressed Than NY-ESO-1 in a Systematic Immunohistochemical Analysis of 3668 Cases, by S.P. Kerkar, Z.F. Wang, J. Lasota, et al (Journal of Immunotherapy, 2016).

The study

• Authors: S.P. Kerkar, Z.F. Wang, J. Lasota, T. Park, K. Patel, E. Groh, S.A. Rosenberg, M.M. Miettinen
• Journal: Journal of Immunotherapy
• Published: 2016;39(4):181-7
• Cited by: 61 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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 NY-ESO-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 MAGE-A, 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.

In plain English

This laboratory study did not examine asbestos exposure. The authors stained tumor samples for two proteins, NY-ESO-1 and MAGE-A, which are being studied as targets for immune-based cancer treatments. They tested 3668 tumors of 29 types on tissue arrays. These included 189 mesotheliomas; the article does not say whether they were pleural or peritoneal. They also tested separate samples of metastatic cancer from patients referred to the NIH for treatment trials. Across all 3668 tumors, 123 (3.4%) stained positive for NY-ESO-1 and 815 (22.2%) for MAGE-A. Among the mesotheliomas, 2 of 189 (1%) were positive for NY-ESO-1 and 25 of 189 (13.2%) for MAGE-A, with 15 (7.9%) staining in more than half of tumor cells. MAGE-A staining was most frequent in seminomas, at 73.5% (83/113). The authors reported that MAGE-A was significantly more often present than NY-ESO-1 in most cancer types. They concluded that MAGE-A may be an immunotherapy target that could benefit many patients. They said future studies must test whether MAGE-A levels predict treatment response.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory immunohistochemistry (tissue staining) study of tumor samples on tissue arrays, plus whole-slide staining of a separate set of metastatic tumors
• Who was studied: 3668 tumor samples of 29 types on tissue arrays, taken mainly from primary sites of disease, including 189 mesotheliomas. A separate set of metastatic carcinomas and metastatic squamous cell carcinomas came from patients referred to the NIH for evaluation for trial eligibility. Dates are not given.
• Exposure: No asbestos or other environmental exposure was studied. The study measured antibody staining for two cancer-testis antigens, NY-ESO-1 and MAGE-A, in tumor tissue.
• Main results:
  • All 3668 array tumors: MAGE-A was positive in 815 (22.2%), and 656 (17.9%) were high expressers (more than 50% of tumor cells staining).
  • All 3668 array tumors: NY-ESO-1 was positive in 123 (3.4%), and 66 (1.8%) were high expressers.
  • Mesotheliomas: NY-ESO-1 was positive in 2 of 189 (1%).
  • Mesotheliomas: MAGE-A was positive in 25 of 189 (13.2%), with 15 (7.9%) showing more than 50% tumor cell staining. The table marks this as significantly higher than NY-ESO-1 (P less than 0.05).
  • Highest MAGE-A positivity: seminoma germ cell tumors 73.5% (83/113), esophageal squamous cell carcinoma 61.5% (16/26), cutaneous squamous cell carcinoma 55.6% (20/36).
  • Highest NY-ESO-1 positivity: gastric adenocarcinomas, 7 of 50 (14%).
  • MAGE-A expression was significantly higher than NY-ESO-1 in the majority of cancer types examined.
  • Metastatic carcinomas: no NY-ESO-1 staining in 35 sections. MAGE-A was positive in 6 of 37 (16%), with high expression in 5 of 37 (13.5%).
  • Metastatic squamous cell carcinomas: NY-ESO-1 was positive in 2 of 28 (7.1%), with high expression in 1 of 28 (3.6%). MAGE-A was positive in 11 of 22 (50%), with high expression in 10 of 22 (45.5%).
• The authors' conclusion: The authors concluded that only a small percentage of patients with common carcinomas may benefit from targeting NY-ESO-1. In contrast, they concluded that MAGE-A is more widely expressed and represents an immunotherapy target that may benefit a large number of patients with various cancer types.
• Limitations the authors state:
  • The authors stated that the apparent link between squamous differentiation and higher MAGE-A expression needs further study.
  • The authors stated that it is not yet known whether the degree of MAGE-A expression predicts response to MAGE-A-targeted therapy.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Throat and laryngeal cancer.

Medical terms in this study, explained in our Lexicon: Squamous Cell Carcinoma, Immunotherapy, Carcinoma, Germ Cell Tumor, Lung Adenocarcinoma, Adenocarcinoma, Mesothelioma.

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