Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma.

Abstract

BACKGROUND:

The unique expression pattern and immunogenic properties of cancer/testis antigens make them ideal targets for immunotherapy of cancer. The MAGE-A3 cancer/testis antigen is frequently expressed in non-small cell lung cancer (NSCLC) and vaccination with MAGE-A3 in patients with MAGE-A3-positive NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC.

METHODS:

Tumor biopsies from normal lung tissue and from a large cohort (n = 169) of NSCLC patients were examined for GAGE, NY-ESO-1 and SP17 protein expression by immunohistochemical analysis. The expression of these antigens was further matched to clinical and pathological features using univariate cox regression analysis.

RESULTS:

GAGE and NY-ESO-1 cancer/testis antigens were not expressed in normal lung tissue, while SP17 was expressed in ciliated lung epithelia. The frequency of GAGE, NY-ESO-1 and SP17 expression in NSCLC tumors were 26.0% (44/169), 11.8% (20/169) and 4.7% (8/169), respectively, and 33.1% (56/169) of the tumors expressed at least one of these antigens. In general, the expression of GAGE, NY-ESO-1 and SP17 was not significantly associated with a specific histotype (adenocarcinoma vs. squamous cell carcinoma), but high-level GAGE expression (>50%) was more frequent in squamous cell carcinoma (p = 0.02). Furthermore, the frequency of GAGE expression was demonstrated to be significantly higher in stage II-IIIa than stage I NSCLC (17.0% vs. 35.8%; p = 0.02). Analysis of the relation between tumor expression of GAGE and NY-ESO-1 and survival endpoints revealed no significant associations.

CONCLUSION:

Our study demonstrates that GAGE, NY-ESO-1 and SP17 cancer/testis antigens are candidate targets for immunotherapy of NSCLC and further suggest that multi-antigen vaccines may be beneficial.

• Authors: Morten F Gjerstorff, Mette Pøhl, Karen E Olsen, Henrik J Ditzel
• Journal: BMC cancer (BMC Cancer) Vol. 13 Pg. 466 (Oct 08 2013) ISSN: 1471-2407 [Electronic] England
• PMID: 24103781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Antigens, Surface
• CTAG1B protein, human
• Calmodulin-Binding Proteins
• Carrier Proteins
• Membrane Proteins
• SPA17 protein, human

Topics

• Antigens, Neoplasm (genetics, metabolism)
• Antigens, Surface (genetics, metabolism)
• Calmodulin-Binding Proteins
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, mortality, pathology)
• Carrier Proteins (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics, metabolism, mortality, pathology)
• Male
• Membrane Proteins (genetics, metabolism)
• Neoplasm Staging
• Prognosis
• Testis (metabolism)