Poorly differentiated carcinoma of the thyroid: validation of the Turin proposal and analysis of IMP3 expression

Abstract

The Turin Proposal algorithm defines poorly differentiated carcinoma on the basis of the presence of solid/trabecular/insular growth pattern, absence of conventional nuclear features of papillary carcinoma, and the presence of at least one of the following features: convoluted nuclei, mitotic activity > or =3/10 HPF, or tumor necrosis. IMP3 appears to have diagnostic and prognostic value in many solid tumors, including thyroid carcinomas. We examined a series of follicular-cell carcinomas with prominent solid patterns diagnosed at Mayo Clinic (56 cases) (Rochester, MN, USA) and at the University of Turin (96 cases) (Northern Italy) to validate the Turin consensus criteria defining poorly differentiated carcinoma of the thyroid and to evaluate the prevalence and prognostic behavior of this tumor. On this series, we analyzed the expression of conventional markers by immunohistochemistry and we investigated the expression of IMP3 by both immunohistochemistry and qRT-PCR. The prevalence of poorly differentiated carcinoma among the USA cases was 1.8% (56/3128) and that in the cases of Northern Italy was 6.7% (96/1442). Tumor characteristics were similar in the cases from the USA and from Italy except for extensive vascular invasion and a prevalent insular growth pattern (lower the former, higher the latter in the Italian series). In univariate analysis, the risk of death was higher for age > or =45, tumors > or =4 cm, and IMP3 positivity. Multivariate analysis showed that the risk of death from poorly differentiated carcinoma was higher for age > or =45. The Turin consensus criteria can reliably select poorly differentiated carcinomas. Tumors from the USA and from Italy showed similar overall survival, although the prevalence of poorly differentiated carcinoma was higher in Northern Italy. Expression of IMP3 appears to be an adverse prognostic factor for poorly differentiated thyroid carcinoma.