NY-ESO-1 Expression and Immunogenicity in Esophageal Cancer

Abstract

Purpose: Although NY-ESO-1 was isolated from an esophageal carcinoma patient, its expression in this type of cancer and its immunogenicity in esophageal cancer patientshave not yet been fully elucidated. We report here the frequency of NY-ESO-1 mRNA and protein expression in esophageal cancer and the presence of NY-ESO-1-specific immune response in patients.Experimental Design: One hundred twenty three esophageal squamous cell carcinoma specimens were analyzed for the expression of NY-ESO-1 mRNA by conventional and real-time reverse transcription-PCR and the expression of protein by immunohistochemistry and Western blot. Sera and peripheral blood lymphocytes from 51 patients were analyzed for the NY-ESO-1 antibody production by enzymelinked immunosorbent assay and NY-ESO-1 T cell response by enzyme-linked immunospot assay. Survival analyses were also performed.Results: NY-ESO-1 mRNA was expressed in 41 of 123 (33%) esophageal squamous cell carcinoma specimens, and its expression was found at higher frequency in well-differentiated and moderately differentiated type of cancer. No mRNA copy was detected in any of the adjacent normal tissues. Twenty-one of 24 (87.5%) NY-ESO-1 mRNA-positive tumors were stained positively by immunohistochemistry. Correlation between the level of NY-ESO-1 mRNA expression and the degree of immunohistochemistry positivity was observed. Antibody production was observed in 2 patients with tumors that showed protein expression. Furthermore, a CD8 T-cell response against NY-ESO-1 was observed in 1 of the 2 seropositive patients.Conclusions: The high expression frequency of NY-ESO-1 mRNA and protein indicates NY-ESO-1 as a feasible vaccine target in esophageal cancer.

Cancer/testis antigen CT45: Analysis of mRNA and protein expression in human cancer

“…This last observation is similar to the findings in NY-ESO-1 by us and other groups. 29,30 On the other hand, similar to other CT antigens, discrepancies between CT45 mRNA and protein expression were observed in sporadic cases, most likely due to sampling error of the tumor and reflected the focal nature of CT expression in cancer. For this reason, we believe that the frequency of CT antigen expression that we observed in this study based on IHC analysis of tissue microarrays of lung cancer (13% positive), ovarian cancer (37%) and breast cancer (<5%) undoubtedly represents the minimal frequency of CT45 expression in these tumor types, and the actual expression frequency is likely 1.5-fold of the observed frequency above, as estimated from the mRNA studies of lung cancer and ovarian cancer.…”

Identification of CCDC62‐2 as a novel cancer/testis antigen and its immunogenicity

“…In a large scale ELISA survey of 191 sera samples from patients with several 26,27 In the Japanese population, around 7% of bladder cancer patients and 4% of esophageal cancer patients showed NY-ESO-1 antibody responses. 28,29 In antibody positive patients, strong CD4 and CD8 responses against NY-ESO-1 were also elicited. 30,31 We have shown similar antibody responses in patients with XAGE-1b-expressing lung cancer.…”

Cancer-testis gene expression profiling in esophageal squamous cell carcinoma: Identification of specific tumor marker and potential targets for immunotherapy

“…However, the lack of sufficient data on the expression profiles of CTAs in esophageal cancer points to a need for a detailed study prior to their application as targets for a cancer vaccine. Few reports have predominantly focused on the protein expression of CTAs [20][21][22][23] and, to some extent, mRNA expression with conventional methods. [24][25][26][27] In this study, we applied the more sensitive and accurate technique of real-time PCR and demonstrated a high frequency of MAGE-A4, NY-ESO1 and LAGE1 overexpression in ESCC.…”