Olfactory receptor 51E1 protein as a potential novel tissue biomarker for small intestine neuroendocrine carcinomas
2013 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 168, no 2, 253-261 p.Article in journal (Refereed) Published
OBJECTIVE: Late diagnosis hinders proper management of small intestine neuroendocrine carcinoma (SI-NEC) patients. The olfactory receptor, family 51, subfamily E, member 1 (OR51E1) has been reported as a potential novel SI-NEC marker, without protein expression recognition. Thus, we further studied whether the encoded protein may be a novel SI-NEC clinical biomarker.
DESIGN: OR51E1 coding sequence was cloned using total RNA from SI-NEC patient specimens. Quantitative real-time PCR analysis explored OR51E1 expression in laser capture microdissected SI-NEC cells and adjacent microenvironment cells. Moreover, immunohistochemistry investigated OR51E1 protein expression on operation and biopsy material from primary SI-NECs, mesentery, and liver metastases from 70 patients. Furthermore, double immunofluorescence studies explored the potential co-localization of the vesicular monoamine transporter 1 (SLC18A1, generally referred to as VMAT1) and OR51E1 in the neoplastic cells and in the intestinal mucosa adjacent to the tumor.
RESULTS: OR51E1 coding sequence analysis showed absence of mutation in SI-NEC patients at different stages of disease. OR51E1 expression was higher in microdissected SI-NEC cells than in the adjacent microenvironment cells. Furthermore, both membranous and cytoplasmic OR51E1 immunostaining patterns were detected in both primary SI-NECs and metastases. Briefly, 18/43 primary tumors, 7/28 mesentery metastases, and 6/18 liver metastases were 'positive' for OR51E1 in more than 50% of the tumor cells. In addition, co-localization studies showed that OR51E1 was expressed in >50% of the VMAT1 immunoreactive tumor cells and of the enterochromaffin cells in the intestinal mucosa adjacent to the tumor.
CONCLUSION: OR51E1 protein is a potential novel clinical tissue biomarker for SI-NECs. Moreover, we suggest its potential therapeutic molecular target development using solid tumor radioimmunotherapy.
Place, publisher, year, edition, pages
2013. Vol. 168, no 2, 253-261 p.
Cell and Molecular Biology Cancer and Oncology Endocrinology and Diabetes Gastroenterology and Hepatology
IdentifiersURN: urn:nbn:se:uu:diva-205136DOI: 10.1530/EJE-12-0814ISI: 000315577400023PubMedID: 23184910OAI: oai:DiVA.org:uu-205136DiVA: diva2:640824