SAT-569 Nuclear TGF-β1 Expression Identifies More Aggressive Thyroid Tumors

Abstract

TGF-β1 is a member of the Transforming Growth Factor β (TGF-β) superfamily of cytokines that is involved in proliferation, migration, differentiation and apoptosis of different cell types. This cytokine can act as a tumor suppressor in early stages of cancer, controlling cellular proliferation and growth; however, as cancer progresses, tumor cells lose their sensitivity to the inhibitory effects of TGF-β1, and, together with increased angiogenesis, induces tumor progression. In order to evaluate a possible clinical utility of TGF-β1 staining, we made a Tissue MicroArray (TMA) including 136 benign (113 female, 18 male, 49.1±14.6 years old), 154 malignant (118 female, 28 male, 42.6±17.0 years old) and 11 normal thyroid tissues. The patients were followed-up for 75.3±65 months. There were 122 goiters, 14 follicular adenomas (FA), 138 differentiated thyroid carcinomas (DTC) [73 classic papillary thyroid carcinomas (CPTC), 42 follicular variant of PTC (FVPTC), 23 follicular thyroid carcinomas (FTC)] and 16 poorly differentiated thyroid carcinomas (PDTC). The analysis were performed by Allred Score with two pathologists independent evaluation. Positive/negative score for cytoplasmic TGF-β1 expression was not different between benign and malignant tissues (p=0.4334). For nuclear TGF-β1 expression, the percentage positive/negative score was 90/10% of benign tissues and 71/29% of malignant (p<0.0001). In fact, nuclear positivity decreased according to the tumor dedifferentiation. We found that 91% of normal tissues presented nuclear positivity, decreasing to 90% of the goiters, 86% of the FA, 74% of the DTC and 44% of the PDTC. Nuclear TGF-β1 positive/negative score was able to distinguish PDTC from DTC (p=0.0188), CPTC (p=0.0384), FTC (p=0.0172), AF (p=0.0259) and goiter (<0.0001). Although there was a net correlation between nuclear TGF-β1 positivity with aggressive thyroid tumors, we were unable to demonstrate any relationship with clinical or pathological features of the tumors. In conclusion, our data suggest that evaluation of nuclear TGF-β1 expression may help identify more aggressive thyroid tumors. Sources of Research Support: Foundation for Research of the State of São Paulo (FAPESP) scholarship [grant number 2015/19117-0] to KCP.