ESPE Abstracts (2014) 82 FC13.3


Overexpression of Supressor Tumoral PTEN, but not DREAM, was Detected in Multinodular Goiter in Humans

Amanda Shinzatoa, Antonio M Lerarioa, Debora S Danilovica, Suemi Maruia, Chin J Linb & Ericka B Trarbacha


aLaboratorio de Endocrinologia Celular e Molecular – LIM25, HCFMUSP, Sao Paulo/Sao Paulo, Brazil; bLaboratorio de Patologia Cardiovascular – LIM22, Sao Paulo/Sao Paulo, Brazil

Background: A high proliferative status of thyroid follicular cells and goiter were observed in mutants mice with Pten−/− or Dream overexpression. In humans, patients with Cowden disease have goiters or other thyroid abnormalities associated with germ-line PTEN mutations.

Objective and Hypotheses: The aim of this study was to investigate the tissue expression of PTEN and DREAM, as well as germ-line and somatic PTEN and somatic DREAM mutations, in patients with multinodular goiter (MNG) to evaluated the role of these genes in goitrogenesis.

Methods: We investigated 60 MNG patients (55 females). Relative quantification of PTEN and DREAM mRNA from hyperplastic thyroid tissue was evaluated by real-time PCR. PTEN and DREAM over and lower expression were respectively defined by value ≥2.0- and ≤0.5-fold. Mutations analyses were performed by PCR amplification followed by automatic sequencing. RQM, relative quantification median.

Results: We observed a high expression of PTEN in 56.7% of MNG with RQM of 3.3 (S.D.=1.4), and only one case with lower expression (RQ=0.27). In the remaining cases (41.7%), PTEN expression was normal (RQM=1.30; S.D.=0.33). In fact, PTEN had been shown to be overexpressed in benign proliferative and typical endometrium hyperplasia, with loss expression related only to carcinomas and precancerous lesions. For the DREAM gene, the most cases of MNG (63.4%) had normal expression with RQM of 1.21 (S.D.=0.37). Over and lower expression of this gene were observed in 28.3% (RQM=3.5; S.D.=5.7) and 10% (RQM=0.4; S.D.=0.14) of the cases, respectively. Regarding PTEN and DREAM mutations analysis, only previously described intronic polymorphisms were observed in DNA from blood and/or thyroid hyperplastic tissue.

Conclusions: Our results demonstrated that PTEN expression is higher in MNG suggesting that this gene is overregulated (or at least has its expression maintained) in this benign hyperplastic thyroid lesions. No evidence for the involvement of DREAM in pathogenesis of human goiters was observed.

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