Development Of Papillary Thyroid Carcinoma Research Articles

Identification of differentiated functional modules in papillary thyroid carcinoma by analyzing differential networks.

The incidence of papillary thyroid carcinoma (PTC) has dramatically increased over the past two decades. This study aimed to investigate the disparity of gene expression between PTC and normal tissues. Gene chip data of E-GEOD-33630 and E-GEOD-60542 were acquired and downloaded from European Bioinformatics Institute Part of the European Molecular Biology Laboratory website. E-GEOD-33630 data contained 94 test samples (49 PTC and 45 normal tissues), and E-GEOD-60542 data contained 63 test samples (33 PTC and thirty normal tissues). The two sets of data were analyzed by screening differential co-expression network (DCN) and identifying M-differential module. Three differential modules were gained after statistical comparison between the PTC and normal tissues (P < 0.05). Short coiled-coil protein (SCOC) gene was as the seed gene of module 1, which contained 7 nodes and 9 edges. Moreover, SYPL1 was the seed gene of module 2 with 10 nodes and 16 edges. THAP1 was the seed gene of module 3 that contained 9 nodes and 12 edges. Analysis and statistical comparison of the gene chip can effectively screen out differential expression genes between the PTC and normal tissues. Based on a large number of samples and gene chip detection, three seed genes of SCOC, SYPL1, and THAP1 are determined. These data provide novel insights into the pathogenesis of PTC. Significant changes in the expression levels between PTC and normal tissues suggest that SCOC, SYPL1, or THAP1 may play a vital role in the incidence and development of PTC, which serve as potential biomarkers for the diagnosis of PTC.

Transcriptomic signature associated with carcinogenesis and aggressiveness of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the fastest-growing disease caused by numerous molecular alterations in addition to previously reported DNA mutations. There is a compelling need to identify novel transcriptomic alterations that are associated with the pathogenesis of PTC with potential diagnostic and prognostic implications.Methods: We gathered and compared 242 expression profiles between paired PTC and adjacent normal tissues and identified and validated the coding and long non-coding RNAs (lncRNAs) associated with the extrathyroidal extension (ETE) of 655 PTC patients in two independent cohorts, followed by predicting their interactions with drugs. Co-expression, RNA interaction, Kaplan-Meier survival and multivariate Cox proportional regression analyses were performed to identify dysregulated lncRNAs and genes that correlated with clinical outcomes of PTC. Alternative splicing (AS), RNA circularization, and editing were also compared between transcriptomes to expand the repertoire of molecular alterations in PTC.Results: Numerous genes related to cellular microenvironment and steroid hormone response were associated with the ETE of PTC. Drug susceptibility predictions of the expression signature revealed two highly ranked compounds, 6-bromoindirubin-3'-oxime and lovastatin. Co-expression and RNA interaction analysis revealed the essential role of lncRNAs in PTC pathogenesis by modulating extracellular matrix and cell adhesion. Eight genes and two novel lncRNAs were identified that correlated with the aggressive nature and disease-free survival of PTC. Furthermore, this study provided the transcriptome-wide landscape of circRNAs in PTC and uncovered dissimilar expression profiles among circRNAs originating from the same host gene, suggesting the functional complexity of circRNAs in PTC carcinogenesis. The newly identified AS events in the SERPINA1 and FN1 genes may improve the sensitivity and specificity of these diagnostic biomarkers.Conclusions: Our study uncovered a comprehensive transcriptomic signature associated with the carcinogenesis and aggressive behavior of PTC, as well as presents a catalog of 10 potential biomarkers, which would facilitate PTC prognosis and development of new therapeutic strategies for this cancer.

Hashimoto's thyroiditis, nodular goiter or follicular adenoma combined with papillary thyroid carcinoma play protective role in patients.

Papillary thyroid carcinoma (PTC) is often combined with other types of thyroid disease, such as Hashimoto's thyroiditis(HT), nodular goiter(NG), Follicular adenoma(FA) and other types. However, the function of these diseases in PTC tumorigenesis and development is not well understood. In this research, 563 PTC patients were recruited and divided into two groups according to pathological diagnosis, namely simple PTC (PTC) and PTC combined with other thyroid diseases (PTC+). Clinicopathological characteristics and BRAFV600E mutation status were compared between PTC and PTC+. Our data showed that there was a statistically significant difference in gender (P=0.007), tumor diameter (5mm, P=0.012; 1cm, P=0.042), lymph node metastasis (P=0.000) and BRAFV600E mutation status (P=0.001) between PTC and PTC+. PTC+ patients have lower lymph node metastasis rate, even if PTC nodule diameter is larger than 5mm (P=0.005) or ≥1cm (P=0.049) or BRAFV600E is mutated (P=0.001). In conclusion, our study suggests that HT, NG and FA, are protective factors of PTC patients, and PTC+ patients have lower lymph node metastasis and BRAFV600E mutation rate compared with simple PTC patients.

BRAF-Oncogene-Induced Senescence and the Role of Thyroid-Stimulating Hormone Signaling in the Progression of Papillary Thyroid Carcinoma.

Oncogene-induced senescence (OIS) explains the phenomenon of cellular senescence triggered by the action of oncogenes. It is a mechanism adopted by a cell to inhibit progression of benign tumors into malignancy, occurs in premalignant lesions, and is almost never present in malignant lesions. BRAF mutations occur in about 40-45% of all papillary thyroid carcinomas (PTCs) and of which 99.7% is the BRAFV600E mutation. A unique phenotype of the BRAFV600E mutation is the upregulation of the thyroid-stimulating hormone receptor (TSHR) on thyrocyte membranes. Despite the overexpression of the receptor, BRAFV600E cells undergo cell cycle arrest leading to OIS via a negative feedback signaling mechanism. A simultaneous increase in serum thyroid-stimulating hormone (TSH) in response to hypothyroidism (common in autoimmune diseases such as Hashimoto's thyroiditis) would cause senescent tumor cells to overcome OIS and proceed towards malignancy, hence showing the importance of TSH/TSHR signaling in the development of PTCs. Increase in TSH/TSHR signaling triggers an increase in levels of downstream enzymes such as manganese superoxide dismutase (MnSOD) and dual-specific phosphatase 6 (DUSP6) which eventually results in the production of oncogenic proteins such as c-Myc. Therefore, the detection of these genetic alterations as effective biomarkers for premalignant lesions of PTC is important in clinical settings and techniques such as polymerase chain reaction-mediated restriction fragment length polymorphism (PCR-RFLP) and real-time PCR can be used to detect the BRAFV600E point mutation and overexpression of TSHR, MnSOD, and DUSP6, respectively.

MicroRNA-144 inhibits proliferation by targeting WW domain-containing transcription regulator protein 1 in papillary thyroid cancer.

Papillary thyroid carcinoma (PTC), the most common histological subtype of thyroid cancer, accounts for between 80 and 90% of all thyroid cancer cases. Previous studies have suggested that microRNAs (miRNAs/miRs) are involved in the development of PTC. The aim of the present study was to investigate whether miR-144 inhibits cellular proliferation in PTC. The expression of miR-144 was detected in PTC and corresponding adjacent non-cancerous tissues, and in the PTC cell line IHH4, using reverse transcription-quantitative polymerase chain reaction. Associations between miR-144 expression levels and the clinicopathological characteristics were analyzed. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of miR-144 expression, and the potential function of miR-144 was investigated in IHH4 cells using a Cell Counting Kit-8 and colony formation assays. Western blotting was applied to analyze the expression level of WW domain-containing transcription regulator 1 (WWTR1) in PTC tissues. miR-144 was significantly downregulated in PTC tissues and the PTC cell line. Low expression of miR-144 was associated with larger tumor sizes (P<0.001). The ROC curves demonstrated that miR-144 may be a potential biomarker for identifying PTC and non-cancerous diseases (sensitivity, 58.7%; specificity, 87.3%) as well as to differentiate PTC with tumor sizes ≥2 cm (sensitivity, 79.2%; specificity, 69.2%). Upregulation of miR-144 significantly suppressed proliferation in IHH4 cells. WWTR1 was overexpressed in PTC tissues compared with in adjacent non-cancerous tissues, and the ectopic expression of miR-144 downregulated WWTR1 in IHH4 cells. Co-transfection with pcDNA-WWTR1 and miR-144 ‘rescued’ the proliferation inhibition. The results of the present study collectively demonstrated that miR-144 is downregulated in PTC, that low expression levels of miR-144 are associated with larger tumor sizes and that miR-144 inhibits cellular proliferation in PTC by targeting WWTR1.

Predictive Value of Sphingosine Kinase 1 Expression in Papillary Thyroid Carcinoma.

Sphingolipid metabolites are emerging as key signaling molecules in cancer. Sphingosine kinase 1 is up-regulated in many different types of human malignancies and plays a crucial role in cancer development and progression. The utility of sphingosine kinase 1 to act as a predictive biomarker in thyroid cancer remains unclear. Sphingosine kinase 1 expression was evaluated using immunohistochemical staining in 110 formalin-fixed, paraffin-embedded papillary thyroid carcinoma tissue samples. Sphingosine kinase 1 expression in papillary thyroid carcinoma tissue was significantly higher than in nodular goiter (p<0.001) or normal thyroid (p<0.001) tissue. Sphingosine kinase 1 was observed in the cytoplasm of tumor cells. Thirty-four (30.9%) of 110 papillary thyroid carcinomas exhibited high sphingosine kinase 1 expression, that was significantly associated with tumor multiplicity (p=0.004), extrathyroidal extension (p=0.013), presence of lymph node metastasis (p<0.001), and number of metastatic lymph nodes (p=0.042). In addition, high sphingosine kinase 1 expression was the only independent predictor of lymph node metastasis (p<0.001). Sphingosine kinase 1 is involved in papillary thyroid carcinoma development and progression and can serve as a potential biomarker predictive of lymph node metastasis.

Higher expression level of tyrosine kinase‑like orphan receptor 2 and Wnt member 5a in papillary thyroid carcinoma is associated with poor prognosis

The tyrosine kinase-like orphan receptor 2 (ROR2) has a wnt-mediated, pro-tumorigenic role in certain types of cancer. The present study was designed to assess the protein expression level of ROR2 and its putative ligand Wnt member 5a (Wnt5a), as well as the association with clinicopathological features in papillary thyroid carcinoma (PTC). A total of 58 patients were recruited, resulting in 58 human PTC tissue samples and their paired adjacent noncancerous tissue samples being obtained. The protein expression levels of ROR2 and Wnt5a were evaluated by immunohistochemistry and western blotting, and messenger RNA expression levels were determined by reverse transcription-quantitative polymerase chain reaction. ROR2 and Wnt5a protein and mRNA expression were significantly overexpressed in PTC tissues (P<0.05). The present study also revealed that ROR2 and Wnt5a were significantly associated with tumor stage and lymph node metastasis (P<0.05). There was a positive association between ROR2 and Wnt5a expression levels (r=0.857; P=0.007). In conclusion, ROR2 and Wnt5a may act as tumor suppressor genes in the development of PTC; overexpression of ROR2 and Wnt5a in PTC may be important for tumorigenesis and tumor development.

Ultrasound variants of autoimmune thyroiditis in children and adolescents and their clinical implication in relation to papillary thyroid carcinoma development

BackgroundThe prevalence of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) is rising in children and adolescents, and the coincidence of AIT and PTC is as high as 6.3–43%.ObjectiveTo investigate the ultrasound manifestation of AIT in relation to PTC development in paediatric patients.Patients179 paediatric patients (133 females), mean (SD) age: 13.9 (3.03) years diagnosed with AIT and referred for ultrasound evaluation. Eight patients were diagnosed with PTC (6 females).MethodsRetrospective analysis of thyroid ultrasound scans of patients diagnosed with AIT. Thyroid and autoimmune status was assessed based on TSH, fT4, fT3 and increased aTPO and/or aTG and/or TRAB levels. In patients with PTC, total thyroidectomy was performed.ResultsAnalysis of thyroid US scans revealed that the following five ultrasound variants of AIT were observed in 179 patients: the most common in 35.2%—diffuse thyroiditis with hypoechogenic background and normoechogenic parenchyma, in 30.2%—diffuse thyroiditis with irregular background, in 18.9% nodular variant with normoechogenic background, in 11.7%—micronodulations and in 3.9%—diffuse hypoechogenic background. Eight cases of PTC were diagnosed in nodular variant of AIT with normoechogenic irregular background.ConclusionPatients with AIT and nodular variant with normoechogenic irregular background of the thyroid gland on US scans are in the risk group of developing PTC and should be followed up with regular neck US assessment.

Activation of the ROCK1/MMP-9 pathway is associated with the invasion and poor prognosis in papillary thyroid carcinoma

Rho-associated protein kinase 1 (ROCK1), aserine/threonine kinase, has previously been shown to be over-expressed in various types of human malignant tumors and to play an important role in cancer development and progression. Although ROCK1 has gained growing prominence as an important protein kinase in cancer biology, its potential as a predictive biomarker and a therapeutic target in papillary thyroid carcinoma (PTC) remains unknown. In the present study, ROCK1 expression was examined in 356 formalin-fixed, paraffin-embedded papillary thyroid carcinoma tissues using immunohistochemistry, and its clinical implications and prognostic significance were analyzed. Our results showed that ROCK1 expression was significantly increased in PTC compared with normal tissues, and was significantly associated with tumor size, lymphatic metastasis, distant organ metastasis, extrathyroid invasion, vascular invasion and tumor, node and metastasis (TNM) stage. Patients with strong ROCK1 expression had lower overall survival, disease-free survival, lymph node recurrence-free survival and distant recurrence-free survival rates than those with weak expression. Furthermore, overexpression of ROCK1 in papillary thyroid carcinoma cells was found to increase their invasiveness. Silencing ROCK1 by siRNA, however, caused an inhibition of cell invasion. Knockdown of ROCK1 decreased the volume and weight of the xenograft tumors, while overexpression of ROCK1 showed a proliferative tendency with significantly greater tumor volume and weight invivo. Moreover, the upregulation of ROCK1 increased the expression of MMP-9, and levels of MMP-9 positively correlated with the ROCK1 levels in PTC tissues, implicating that MMP-9 may be involved in the mechanism of ROCK1 in the development and progression of PTC. These data suggest that ROCK1 might be a potential prognostic marker and therapeutic target for the treatment of PTC.

LAPTM4B*2 allele is associated with the development of papillary thyroid carcinoma in Chinese women.

Lysosome-associated protein transmembrane 4-β (LAPTM4B) contains a polymorphic region that contributes to the increased risk of numerous types of tumor. However, no study has yet demonstrated an association between the expression of the LAPTM4B gene and tumor differentiation, and the reason that LAPTM4B polymorphisms affect the susceptibility of individuals to cancer remains to be elucidated. The present study assessed the possible association between LAPTM4B polymorphism and the risk of papillary thyroid carcinoma (PTC), and attempted to identify the underlying mechanism for variation in patient susceptibility with respect to transcription regulation in the polymorphism region. The case control study included 183 papillary thyroid carcinoma patients (132 females, 51 males) and 697 healthy controls (249 females, 448 males). Genomic DNA was extracted from the blood and the genotype of LAPTM4B was identified using polymerase chain reaction (PCR). The results of the PCR revealed that LAPTM4B allele *2 was associated with PTC risk in comparison with LAPTM4B allele *1 [odds ratio (OR), 1.968; 95% confidence interval (CI), 1.363–2.841, P<0.001] in females, while LAPTM4B*2 was not associated with PTC risk in males (OR, 0.996, 95% CI, 0.615–1.612, P=0.986). Notably, LAPTM4B polymorphism was not associated with clinical parameters in the female patient group. In addition, by performing a luciferase reporter assay in the PTC TPC1 and B-CPAP cell lines, the transcriptional activity of the +10/+311 plasmid, representing LAPTM4B*2 was reduced compared with that of the +10/+292 plasmid representing LAPTM4B*1. In conclusion, the results of the present study suggested that LAPTM4B*2 was a susceptibility factor for PTC in the female Chinese population and this may not be caused by the transcriptional regulation of LAPTM4B polymorphism region in TPC1 and B-CPAP cell lines.

A meta-analysis of Hashimoto's thyroiditis and papillary thyroid carcinoma risk.

ObjectiveIt remains inconclusive whether Hashimoto’s thyroiditis (HT) predisposes patients to the development of papillary thyroid carcinoma (PTC). We conducted a meta-analysis of the available data to address this question.ResultsTwenty-seven eligible studies were selected, including 18 archival thyroidectomy studies, 6 fine-needle aspiration (FNA) studies, and 3 selective FNA or thyroidectomy studies. A total of 76,281 patients, including 12,476 cases of thyroid cancer, were included in these studies. The mean rate of PTC among patients with HT ranged from 1.12% (selective FNA or thyroidectomy studies) to 40.11% (thyroidectomy studies). All three types of studies supported the correlation between HT and PTC. The overall pooled odds ratio (OR) of the PTC risk for HT (HT versus non-HT) was 2.12 (95% confidence interval [CI]: 1.78-2.52).MethodsWe searched all relevant published studies using the citation databases PubMed and Embase. The ORs and corresponding 95% CIs were calculated by the random-effects model for the association between HT and PTC.ConclusionsOur meta-analysis confirmed that HT predisposed patients to the development of PTC.

Results of randomized phase II trial of dabrafenib versus dabrafenib plus trametinib in BRAF-mutated papillary thyroid carcinoma.

6022 Background: BRAF mutations are present in ~44% of papillary thyroid carcinoma (PTC) and its role in development of PTC is well established. We hypothesized that dabrafenib (BRAF inhibitor) would have efficacy in BRAF mutated PTC and that combining it with trametinib (MEK inhibitor) would result in greater clinical efficacy than dabrafenib alone, through vertical inhibition of the RAF/MAP/ERK pathway and mitigation of potential mechanisms of resistance. Methods: Patients (pts) with BRAF mutated radioiodine refractory PTC who had evidence of disease progression within 13 months prior were randomized to Arm A (dabrafenib 150 mg PO BID) or Arm B (dabrafenib 150 mg PO BID + trametinib 2 mg PO qd). Cross-over to Arm B was allowed at time of progression. Responses were assessed by modified RECISTv1.1 every 2 months. Primary endpoint was objective response rate (ORR) (complete-, partial- and minor-response). With assumed true ORR of 15% vs 35%; and 90% power to identify the correct regimen as most promising, 26 pts were to be accrued in each Arm. Results: In this randomized phase 2 trial, 53 pts (median age 63 years, 38 females) were enrolled; 25% of pts had 1-3 prior therapy with multi-kinase inhibitors. Median follow up was 13 months. Preliminary efficacy results are outlined in Table. The treatment-related adverse events were similar to previously reported phase III clinical trial of these drugs in melanoma. Conclusions: Single agent dabrafenib, as well as combination of dabrafenib/trametinib are well tolerated therapies that result in similar high objective response rates with durable responses in pts with progressive BRAF-mutated PTC. BRAF-pathway targeted therapies provide novel treatment options. Clinical trial information: NCT01723202. [Table: see text]

Development of papillary thyroid carcinoma in a patient with multiple solid cell nests of the thyroid

Development of papillary thyroid carcinoma in a patient with multiple solid cell nests of the thyroid

Expression of autophagy-associated proteins in papillary thyroid carcinoma

The present study was designed to assess the protein expression of the autophagy-associated genes, Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)-II, as well as the association with clinicopathological features in papillary thyroid carcinoma (PTC). A total of 50 subjects were recruited, including 50 human PTC samples and paired adjacent noncancerous tissue samples. The protein expression of Beclin-1 and LC3-II was analyzed using immunohistochemistry and western blotting. Beclin-1 and LC3-II expression in PTC tissues significantly reduced compared with normal tissues (P<0.05). Expression of Beclin-1 and LC3-II was associated with lymph node metastasis of PTC (P<0.05), but had no association with age, gender, tumor size, tumor number and Tumor-Node-Metastasis stage (P>0.05). Expression of Beclin-1 and LC3-II were positively correlated (r=0.327;P=0.020) in PTC. In conclusion, the activity of autophagy was declined in PTC; this decrease in autophagic capacity may be associated with tumorigenesis and the development of PTC.

HABP2 p.G534E variant in patients with family history of thyroid and breast cancer.

Familial Papillary Thyroid Carcinoma (PTC) has been described as a hereditary predisposition cancer syndrome associated with mutations in candidate genes including HABP2. Two of 20 probands from families with history of PTC and breast carcinoma (BC) were evaluated by whole exome sequencing (WES) revealing HABP2 p.G534E. Sanger sequencing was used to confirm the involvement of this variant in three families (F1: 7 relatives; F2: 3 and F3: 3). The proband and his sister (with no malignant tumor so far) from F1 were homozygous for the variant whereas one relative with PTC from F2 was negative for the variant. Although the proband of the F3 with PTC was HABP2 wild type, three relatives presented the variant. Five of 170 healthy Brazilian individuals with no family history of BC or PTC and three of 50 sporadic PTC presented the p.G534E. These findings suggested no association of this variant with our familial PTC cases. Genes potentially associated with deregulation of the extracellular matrix organization pathway (CTSB, TNXB, COL4A3, COL16A1, COL24A1, COL5A2, NID1, LOXL2, MMP11, TRIM24 and MUSK) and DNA repair function (NBN and MSH2) were detected by WES, suggesting that other cancer-associated genes have pathogenic effects in the risk of familial PTC development.

Expression of microRNA-221 and IL-17 in papillary thyroid carcinoma and correlation with clinicopathologic features

Objective: To study the expression of microRNA-221(miR-221) and IL-17 in papillary thyroid carcinoma (PTC) and their roles in the carcinogenesis of PTC. Methods: Real-time RT-PCR, Western blot and immunohistochemistry (IHC) were used to detect the expression of miR-221 and IL-17 in 40 cases of PTC, 20 adjacent normal thyroid tissues and 20 cases of nodular goiter, and the correlation with clinicopathologic features was analyzed. Results: (1)The expression level of miR-221 was significantly higher in PTC compared with nodular goiter and adjacent normal thyroid tissue (P<0.05), but not between the latter two (P>0.05). The expression of miR-221 was related to TNM staging, capsular invasion and lymph node metastasis (P<0.05) but not to patients' age, sex, tumor size, multifocality, tumor spread and vascular invasion.(2)Real-time RT-PCR and Western blot showed that higher levels of IL-17 mRNA and IL-17 protein in PTC than nodular goiter and adjacent normal thyroid tissue (P<0.05), but not between the latter two (P>0.05). IHC assay showed positive expression of IL-17 in PTC but not in nodular goiter and adjacent normal thyroid tissue. IL-17 expression was related to TNM staging, capsular invasion and lymph node metastasis, but not to patients' age, sex, tumor size, tumor spread and vascular invasion.(3) Expression analysis revealed a significant correlation between the miR-221 and IL-17 expression (r=0.524, P=0.001). Conclusions: The expressions of miR-221 and IL-17 are significantly higher and positively correlated in PTC, suggesting that miR-221 may regulate IL-17 expression by interacting with a variety of cytokines and inflammatory cells to participate in the development of PTC. miR-221 may be a potential novel prognostic indicator and therapeutic target for PTC.

CXCL12 methylation-mediated epigenetic regulation of gene expression in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and its incidence rate is rapidly growing. It is necessary to understand the pathogenesis of PTC to develop effective diagnosis methods. Promoter methylation has been recognized to contribute to the alterations in gene expression observed in tumorigenesis. Our RNA-seq data identified 1191 differentially expressed mRNAs and 147 differentially expressed lncRNAs in PTC. Next, promoter methylation of these genes was detected by reduced representation bisulfite sequencing (RRBS) technology and comprehensively analyzed to identify differential methylation. In total, 14 genes (13 mRNAs and 1 lncRNA), in which methylation was intimately involved in regulating gene expression, were proposed as novel diagnostic biomarkers. To gain insights into the relationships among these 14 genes, a core co-function network was constructed based on co-expression, co-function and co-methylation data. Notably, CXCL12 was identified as an essential gene in the network that was closely connected with the other genes. These data suggested that CXCL12 down-regulation in PTC may be caused by promoter hypermethylation. Our study was the first to perform an RRBS analysis for PTC and suggested that CXCL12 may contribute to PTC development by methylation-mediated epigenetic regulation of gene expression.

Expression characteristics of proteins of IGF-1R, p-Akt, and survivin in papillary thyroid carcinoma patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is related to increased risk of papillary thyroid carcinoma (PTC). Insulin-like growth factor-1 receptor (IGF-1R) is increased in patients with T2DM. The increased IGF-1R may be responsible for the development of PTC. In this study, we investigated the expression of phosphorylation of Akt (p-Akt)/survivin pathway activated by IGF-1R in PTC subjects with and without diabetes.Clinicopathological data of 20 PTC patients with T2DM were retrospectively analyzed and compared with those of 21 PTC subjects without diabetes. Meanwhile, IGF-1R, p-Akt, and survivin expressions of PTC tissues were detected by immunohistochemical staining.The immunohistochemical results found that the expression level of IGF-1R was significantly higher in diabetic PTC patients than that in nondiabetic PTC patients (P < 0.05). However, no significant differences of p-Akt and survivin expression were found between PTC patients with T2DM and PTC patients without T2DM. In addition, among 20 PTC patients with T2DM, subgroup analysis showed that the ratio of tumor size >10 mm was significantly higher in IGF-1R moderate to strong expression group than that in IGF-1R negative to weak expression group (P < 0.05).IGF-1R expression level was higher in PTC patients with T2DM, and the increased IGF-1R expression was associated with lager tumor size. IGF-1R may play an important role in carcinogenesis and tumor growth in PTC patients with T2DM.

Exploring the Relationship Between Bisphenol A, Iodine and Papillary Thyroid Carcinoma

Bisphenol A, one of the environmental endocrine disrupting chemicals, was shown to have a weak estrogen activity and could disrupt thyroid function to some degree. Iodine, which is the most essential microelement that is used for the synthesis of thyroid hormones in humans, was proven to give rise to thyroid diseases, such as thyroiditis, thyroid nodular goiter, and so on. There are relatively very few studies that have considered the role that both Iodine and Bisphenol A play in the development of papillary thyroid carcinoma. Therefore, this crosssectional observational study was carried out to explore the relationship between Iodine, Bisphenol A and Papillary Thyroid Carcinoma. The study included 113 subjects aged from 20 years to 80 years selected from Qilu Hospital of Shandong University from February 2015 to September 2015 and 65 healthy volunteers residing in Jinan, P.R. China. We compared the differences of the concentrations of Urinary Iodine, Urinary Bisphenol A and Serum Bisphenol A among patients of Papillary Thyroid Carcinoma, nodular goiter and normal population. In the PTC and nodular goiter group, urinary BPA and Iodine concentrations were significantly higher than controls stating that the excretion of Iodine and BPA were increased. Meanwhile 23 patients with papillary thyroid carcinoma (43%) had excessive iodine nutrition compared to only 6 volunteers with excessive iodine intake in the control group (9%). These findings suggest that excessive dietary iodine intake is a risk factor for thyroid cancer. Moreover, the significant association between urinary creatine-adjusted BPA and iodine suggest that they might have a synergistic effect on the thyroid.&#x0D; JCMCTA 2016 ; 27 (2) : 50 - 59

Histologic Findings and Cytological Alterations in Thyroid Nodules After Radioactive Iodine Treatment for Graves' Disease: A Diagnostic Dilemma.

Unlike the well-documented relation between radiation to the neck and development of papillary thyroid carcinoma, a causal association between radioactive iodine treatment for Graves' disease and development of thyroid malignancy is less defined. However, patients with a background of thyroid dysfunction presenting with clinically palpable thyroid nodules are followed more closely than the average population, and fine needle aspiration is recommended in such circumstances. Cytological examination of aspirates, and histologic examination of tissue provided from patients with a known history of Graves' disease, managed by radioactive iodine therapy can create a diagnostic dilemma, as the distinction between radiation effect and a malignant primary thyroid neoplasm can be very challenging. Thus, pathologists should be aware of the existence of these changes in the setting of radiation therapy for Graves' disease. Providing pathologists with appropriate clinical history of Graves' disease treated with radioactive iodine is of paramount importance in order to prevent an overdiagnosis of malignancy.