Abstract

Abstract The REarranged in Transfection (RET) tyrosine kinase is important during development of neural crest derived tissues such as the enteric and sympathetic nervous systems, but is also activated in multiple human tumour types. Activating mutations of RET play an important role in thyroid cancers including both papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC). More broadly, recent studies have also shown that RET may be active in other tumour types such as pancreatic and breast cancers, and that the overexpression and activation of RET may be linked to more aggressive disease. In order to explore this link, we have investigated the expression of RET in a large cohort of over 400 thyroid tumour samples of multiple histologies, ranging from benign lesions through to aggressive, metastatic disease by immunhistochemistry using a thyroid tissue microarray. Our data suggest that RET expression may correlate with more aggressive phenotype across a broader spectrum of tumours than previously predicted. We are currently investigating this association further; first by examining the expression of two major RET protein isoforms, RET9 and RET51, in this panel of tumours, and second, by investigating the coexpression of RET with another group of proteins associated with tumour progression, the integrin family. In preliminary studies, we have evaluated RET coexpression with two integrin subunits, ITGB1 and ITGB3. Our data suggest correlation between tumour aggressiveness and coexpression of RET with these integrin subunits. Together, our data provides insight on the role of RET in increasing aggressiveness over a range of tumours. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 943. doi:1538-7445.AM2012-943

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