Gene expression in midgut carcinoid tumors: Potential targets for immunotherapy

Abstract

Classical midgut carcinoids are serotonin-secreting tumors derived from enterochromaffin cells in the gut. Metastatic disease represents a therapeutic challenge and immunotherapy implies a novel approach for treatment. In order to define antigens suitable for T-cell therapy with a preferential expression in midgut carcinoid tissue a broad screening of genes with preferential neuroendocrine restriction, genes described as over-expressed in various malignancies, and genes encoding cancer-testis associated antigens was performed. The expression of 32 genes was analyzed by reverse transcription polymerase chain reaction (RT-PCR) in 28 midgut carcinoid specimens, in the cell line BON and in normal tissues. Immunohistochemistry (IHC) was used to evaluate protein expression. Expression is shown of genes that have previously not been observed in midgut carcinoid tumors, such as Survivin and GAGEs. Also the expression is confirmed of genes that encode pivotal proteins in enterochromaffin cells, such as TPH1 and VMAT1, and their tissue-restricted expression is indicated. In addition, gene expression of IA-2 and CDX-2 in normal gastrointestinal (GI) tract and in tumor is shown. Protein expression of TPH, VMAT1, and Survivin was detected in tumor tissue. This study elucidates that TPH1, VMAT1, and Survivin should be further investigated as potential target antigens for T cell-mediated immunotherapy of midgut carcinoids.