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Paraneoplastic antigen Ma2 (PNMA2) auto-antibodies as biomarkers for early small intestine neuroendocrine tumors detection

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Introduction: Small intestine neuroendocrine tumors (NETs) comprise well-differentiated NET (benign carcinoid), well-differentiated neuroendocrine carcinoma (malignant carcinoid) and poorly differentiated neuroendocrine carcinoma (NEC). The majority of NET patients have developed liver metastases at the time of diagnosis and surgery is then seldom curative. Novel predictive, diagnostic and prognostic markers are thus needed to improve our capabilities to diagnose and cure these tumors. We have previously identified six novel marker genes for neuroendocrine tumor cells by using Affymetrix microarrays and advanced bioinformatics. One of this markers, the paraneoplastic antigen Ma2 (PNMA2), which is normally expressed only in nervous tissue, can in the process of carcinogenesis be detected in tumors located outside the nervous system. The finding that Ma2 is expressed in small intestine neuroendocrine primary tumors and their metastases made it interesting to screen whether antibodies against Ma2 are present in the serum of NET patients.

Aim(s): Novel serum biomarkers for the early detection of small intestine NETs are not currently available. The main objective of this study is to examine the usefulness of PNMA2 auto-antibodies as a novel serum marker in patient sera at different stages of the disease to establish its potential importance in diagnostics.

Materials and methods: PNMA2 gene and protein expression were confirmed by quantitative real-time PCR and immunohistochemistry. PNMA2 auto-antibodies levels as serum-based neuroendocrine small intestine tumor marker were evaluated by a newly developed indirect ELISA assay. A total of 124 serum samples from patients diagnosed with small intestine neuroendocrine primary tumors, lymph node and liver metastases were evaluated. Fifty-two serum samples of typical and atypical lung carcinoids and 50 serum samples of healthy donors were also used as controls. In all statistical analyses (Mann-Whitney U test) p < 0.05 were considered significant.

Conference: 7th Annual ENETSConcerence (2010)

Presenting Author: Giandomenico V

Authors: Cui T, Elgue G, Li S, Hurtig M, Veronesi G,

Keywords: Small intestine neuroendocrine tumors, novel diagnostic biomarker, PNMA2, auto-antibodies as serum biomarker.,

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