Thyroid Tumours Of Follicular Origin Research Articles

Pecularities of cyclin D1 expression in thyroid tumours of follicular origin

Heterogenity of thyroid tumors of follicular origin determines certain differential – diagnostic difficulties both in cytology aspirate, and during the final patho­ logical study. Now the role of various diagnostic/pro­ gnostic markers in the diagnosis of thyroid tumors is extensively studied. Normal follicular cells do not ex­­press cyclin D1, whereas expression in malignant tu­­ mors has been reported in 60-70% of cases. The aim of the study is to determine the expression of cyclin D1 in benign and malignant tumors of thyroid of follicular origin.Materials and methods. Histological preparations of thyroid tumors from28 patients with benign and malignant tumors of the thyroid gland in the period 2011-2012 had been used. The average age of was 42,8±3,9 years (range from 28 to 75 years). According to the results of histopathological study thyroid tumors were divided into 3 groups: benign (10 cases, 35.7%), malignant (10 cases, 35.7%) UMP-T (8 cases, 28.6%). Group of benign tumors made up of AFA (6 cases, 60.0%) and GTT (4 cases, 40.0%), a group of malig­­ nant – FC(4 cases, 40.0%) and PC (6 cases, 60.0% ). The immunohistochemical study was performed using a standard streptavidin-biotin-peroxidase method using a monoclonal antibody at the recommended pro­cedure. The reaction was evaluated semiquantitatively.Results and discussion. Immunohistochemical ex­­pression of cyclin D1 was detected in all thyroid tumors of different grade, but the intensity of ex­­pres­ sion was different. In benign tumors, the expression of cyclin D1 was weak (30%), in malignant – indicators of expression of this marker is higher than 90%. In UMP-tumours cyclin D1 expression was determined in 50% of cases.Conclusions. Obtained results have shown that expression of cyclin D1 may be of prognostic value in the study of the biological behavior of malignant thyroid neoplasms.

Expression of matrix metalloproteinase-2 and its tissue inhibitor-2 in fetal and neoplastic thyroid tissue and their significance as diagnostic and prognostic markers in papillary carcinoma

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have roles in physiological and pathological processes. We evaluated immunohistochemical expression of MMP-2 and TIMP-2 in paraffin sections of 12 human fetal thyroids at mid-term gestation and 79 thyroid tumors of follicular origin. Besides evaluating expression of these proteins during fetal development and neoplastic transformation, we determined whether expression of MMP-2 and TIMP-2 may help to differentiate papillary thyroid carcinoma (PTC) from follicular thyroid adenoma (FTA) and/or peritumoral tissue (PT). We also investigated their relationship with prognostically important clinicopathological parameters of PTC. Immunoreactive MMP-2 and TIMP-2 were found in all fetal thyroid tissues examined. Tumor tissues contained variable amounts of MMP-2 and TIMP-2, with overexpression of these proteins in PTC compared to FTA and PT tissue. According to the statistical analysis, MMP-2 distinguished follicular variant of PTC from FTA and overall PTC from total nonmalignant lesions. In PTC, high MMP-2 expression correlated with lymph node metastasis (P=0.022), while high TIMP-2 expression was positively correlated with tumor size (P=0.049) and extrathyroid invasion (P=0.017). Overall, these results indicate a role for MMP-2 and TIMP-2 in both thyroid development and malignant transformation and suggest that positive immunohistochemistry for MMP-2 and TIMP-2 might support diagnosis of PTC and predict unfavorable biological behavior.

Underexpression of PPARγ is associated with aneuploidy and lower differentiation of thyroid tumours of follicular origin

Peroxisome proliferator-activated receptor gamma (PPARgamma) gene is a nuclear receptor that is involved in thyroid tumourigenesis. Recently, our group has shown that follicular carcinomas underexpressing PPARgamma protein are more prone to develop distant metastases, to invade locally, to present poorly differentiated areas and to persist after surgery. Aneuploidy is also observed in some thyroid tumours, particularly in the more advanced cases. The aim of the present study was to investigate the association of PPARgamma expression with the degree of differentiation and ploidy status of benign and malignant thyroid neoplasias. DNA cytometric studies, ploidy and S-phase fraction (SPF) determination, and quantitative RT-PCR analysis of molecular markers specific for thyroid follicular cells, namely Tg (thyroglobulin), TSHR (TSH receptor) and NIS (Na+/I- symporter) were compared between thyroid lesions with positive or negative PPARgamma protein expression. We observed that PPARgamma-negative tissues expressed lower levels of Tg mRNA [4.66 x 10(6) a.u. (arbitrary units) +/- 1.49 x 10(6)], and were more frequently aneuploid (36%), and presented higher SPF (3.1%+/-0.4) than PPARgamma-positive samples (Tg mRNA = 2.54 x 10(7) a.u. +/- 9.72 x 10(6), P=0.0006; aneuploidy=8%, P=0.0031; SPF=2.2%+/-0.2, P=0.0430). A similar trend was also observed for TSHR and NIS mRNA, although not reaching statistical significance. This study showed that underexpression of PPARgamma is associated with poor tumour differentiation, aneuploidy and higher cell proliferative activity. Therapies designed to modulate expression of PPARgamma may have an impact on the growth of thyroid neoplasias.

Evidence for a 3p25 Breakpoint Hot Spot Region in Thyroid Tumors of Follicular Origin

Epithelial tumors of the thyroid are cytogenetically well-investigated tumors. So far, the main cytogenetic subgroups, characterized by trisomy 7 and by rearrangements of either 19q13 or 2p21, respectively, have been described. Recently, we have been able to describe the involvement of a novel gene called THADA in benign thyroid lesions with 2p21 rearrangements. Other fusion genes found in thyroid lesions are RET/PTC and PAX8/PPAR(gamma). The latter occurs in follicular thyroid carcinomas with a t(2;3)(q13;p25). Here we present molecular-cytogenetic and cytogenetic investigations on a follicular thyroid adenoma with a t(2;20;3)(p21;q11.2; p25). In this case, an intronic sequence of PPAR(gamma) is fused to exon 28 of THADA. We used BAC clones containing the genomic sequence of PPARgamma for fluorescence in situ hybridization to confirm the localization of the breakpoint within intron 2 of PPAR(gamma) . Our findings suggest that the close surrounding of PPAR(gamma) is a breakpoint hot spot region, leading to recurrent alterations of this gene in thyroid tumors of follicular origin including carcinomas as well as adenomas with or without involvement of PAX8.