Cancer–Testis Antigen Expression in Digestive Tract Carcinomas: Frequent Expression in Esophageal Squamous Cell Carcinoma and Its Precursor Lesions

Abstract

Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45, SAGE1, and NXF2] was evaluated by immunohistochemistry in 61 esophageal carcinomas (40 adenocarcinoma and 21 squamous cell carcinoma), 50 gastric carcinomas (34 diffuse and 16 intestinal type), and 141 colorectal carcinomas. The highest frequency of expression was found in esophageal squamous cell carcinomas: Positive staining for MAGEA, CT45, CT7, SAGE1, GAGE, NXF2, NY-ESO-1, and CT10 was observed in 57%, 38%, 33%, 33%, 29%, 29%, 19%, and 14% of squamous cell carcinomas, respectively. Similar staining patterns were observed in squamous dysplasias. Expression frequencies of cancer-testis antigens were seen in 2% to 24% of gastroesophageal adenocarcinomas and were not significantly different between adenocarcinomas of the stomach versus the esophagus, or between diffuse and intestinal types of gastric adenocarcinomas. Colorectal cancers did not express NY-ESO-1, CT7, CT10, or GAGE, and only infrequently expressed SAGE1 (0.7%) MAGEA (1.4%), CT45 (3.5%), and NXF2 (8.5%). We conclude that cancer-testis antigens are frequently expressed in esophageal squamous neoplasms. Although cancer-testis antigens are generally considered to be expressed later in tumor progression, they are found in squamous dysplasias, suggesting a potential diagnostic role for cancer-testis antigens in the evaluation of premalignant squamous lesions. Cancer Immunol Res; 2(5); 480-6. Ó2013 AACR.

Cancer immunoprevention

“…This suggests that raising immunity to one or more of these antigens with a vaccine prior to any evidence of tumor would strengthen immunosurveillance and reduce risk, eventually replacing prophylactic mastectomies. CT antigens have also been found in squamous dysplasia leading to head and neck cancer, and squamous cell carcinoma in situ in esophageal biopsies [24,25], two other cancers that could be targeted for prevention in the premalignant stage.…”

The prevalence and expression pattern of melanoma-associated antigen 1 in esophageal squamous cell carcinoma: a historical cohort study

“…A 2005 study by Liang et al measured the MAGE1 gene expression via RT-PCR and reported the gene overexpression in 25.7% of esophageal SCCs (20). The prevalence of MAGE1 in studies by Haier et al in 2006 and Chen et al in 2014 was 50% and 57% respectively (18, 19). Immunohistochemistry technique was used in these studies, similar to ours (18, 19).…”

“…The prevalence of MAGE1 in studies by Haier et al in 2006 and Chen et al in 2014 was 50% and 57% respectively (18, 19). Immunohistochemistry technique was used in these studies, similar to ours (18, 19). A 2011 study by Forghanifard et al showed that MAGE1 mRNA was overexpressed in 90.2% of esophageal SCC specimens in the Iranian population (29).…”

“…Haier et al reported that MAGE1 was expressed in half of esophageal SCCs; however, they did not find any prognostic value in this context (18). Chen et al and Liang et al showed that this antigen was expressed frequently in SCC of esophagus and was related to tumor progression (19, 20). These controversies still remain unresolved: whether MAGE1 cancer testis antigen has a specific clinicopathologic importance in high incidence areas such as Iran, has yet to be proved.…”

The FDA Guidance on Therapeutic Cancer Vaccines: The Need for Revision to Include Preventive Cancer Vaccines or for a New Guidance Dedicated to Them

“…Many of the tumor antigens targeted by therapeutic cancer vaccines are also expressed in premalignant lesions and immune responses against them can be detected (7–14). In addition, all of the proposed mechanisms of action of therapeutic vaccines, such as development of tumor antigen specific cytotoxic T cells or antibodies and formation of immune memory, are the same as those that are expected of vaccines focused on reducing the risk of developing invasive cancer (15–17).…”