Features Of Papillary Thyroid Cancer Research Articles

Low Vitamin D Status is Not Associated with the Aggressive Pathological Features of Papillary Thyroid Cancer.

Objectives:In the present study, we investigated the effects of Vitamin D (vit D) deficiency on aggressiveness of papillary thyroid cancer (PTC).Methods:Patients with PTC confirmed with pathological examination, whom were operated by a single surgeon between 2012 and 2017, were included in the study. The data of the patients were analyzed retrospectively. Cancers other than PTC, patients with hyperthyroidism and/or using antithyroid drugs were excluded from the study. The patients were classified as four quartiles according to serum Vit D levels; category 1 (<7.1 ng/mL), category 2 (7.2–11.8 ng/mL), category 3 (11.9–23.4 ng/mL) and category 4 (>23.5 ng/mL).Results:A total of 133 patients (103 female, 30 male) with mean age of 46.4±13.6 (17–82) years were included in the study. There was no significant difference between the categories in terms of preoperative Vit D values according to the evaluated tumor aggressiveness characteristics. It was determined that the presence of tumor with a size above 1 cm and T3/4 tumor were not affected by Vit D level. There was no significant difference between Vit D categories regarding the characteristics of aggressiveness such as multicentricity, lymphovascular invasion, central, and lateral metastases.Conclusion:According to our results, serum Vit D levels are not associated with the aggressive tumor characteristics of PTC.

Relationship Between Thyroid-Stimulating Hormone Level and Aggressive Pathological Features of Papillary Thyroid Cancer.

Objectives:Thyroid-stimulating hormones (TSHs) are associated with the risk of differentiated thyroid cancer. The relationship between pre-operative TSH levels and aggressive features is unclear. We aimed to evaluate the relationship between pathological features of papillary thyroid carcinoma (PTC) and high TSH levels.Methods:Patients who were operated between 2012 and 2017 and who were found to have PTC in their pathology were included in the study. The relationship between TSH and the features of tumor aggressiveness was evaluated in the patients.Results:Of the 132 patients, TSH level was significantly higher in those with lymphovascular invasion than those without (p=0.048), in those with central metastases than in those without (p=0.014), and in those with extrathyroidal spread than in those without (p=0.003). When patients were categorized into four 25% quartiles according to TSH (mUI/mL) level; the rate of extrathyroidal invasion increased as the TSH level increased, and the level was significantly higher in quartile 1 than the others, with significant difference (p=0.030).Conclusion:Pre-operative increase in TSH level is associated with an increased risk of extrathyroidal spread and central lymph node metastasis. TSH level may be a pre-operative valuable predictive factor for patients’ risk of central metastasis.

Association between metabolic syndrome and clinicopathological features of papillary thyroid cancer.

BackgroundMetabolic syndrome (MetS) was a risk factor for papillary thyroid cancer (PTC). Whether MetS impacts the aggressiveness of PTC is still unclear. We carried out this study to clarify this issue.MethodsWe evaluated 745 consecutive PTC patients treated with surgery. Patients were divided into three groups based on their number of MetS components: patients without any MetS components, patients with 1–2 MetS components, and patients with 3–5 MetS components. The clinical features and histological aggressiveness of PTC at the time of diagnosis were evaluated.ResultsA total of 745 patients were included in this study. And, 145 patients had three or more metabolic components and were diagnosed as MetS. MetS was a risk factor for larger tumors (OR = 2.29, 95% CI: 1.31–4.03), more lymph node metastasis (OR = 1.97, 95% CI: 1.11–3.51), and later clinical stage (OR = 7.92, 95% CI: 1.59–39.34) after correction for age, sex, and thyroid-stimulating hormone (TSH) level and body mass index (BMI).ConclusionIn our hospital-based cohort study MetS was associated with the aggressiveness of PTC. This association was still significant after adjusting for age, sex, TSH, and BMI.

Cytomorphological features of papillary thyroid carcinomas with the development of radioiodine-resistance

Background. The problem of diagnosis and treatment of papillary thyroid cancer (PTC) are radioiodine resistant metastases (RIRM). An urgent issue is the possibility of their early prediction and diagnosis based on the detection of cytomorphological features of the PTC and its metastases, which correlate with the development of radioiodine (RI) resistance. Purpose – detection of cytomorphological features of primary PTC and its metastases in patients who subsequently showed resistance to 131I therapy, compared with the control group of patients who achieved a positive effect of 131I therapy. Materials and Methods. A comparative analysis of morphological features in histological conclusions and the study of cytological characteristics in the fine-needle aspiration (FNA) smears of primary PTC and their primary metastases, as well RIRM оf experimental and control groups of patients were conducted. The experimental group consisted of 152 patients who showed resistance to RI therapy, the control group – 161 patients who achieved a positive effect of RI therapy. Statistical processing was done in Statistica 12. Results and discussion. It is shown that the frequency of follicular structures in the material of primary PTC of patients with a positive effect of 131I therapy is significantly higher, and the frequency of necrotic changes is significantly lower than in patients with the development of RIRM (p &lt;0.05 by criterion χ2). The frequency of follicular structures in the histological material and FNA smears of primary metastases of patients with a positive effect of 131I therapy is significantly higher, and oxyphilic changes are significantly lower than in patients with the development of RIRM (p &lt;0.05 by criterion χ2). Oxyphilic changes were observed significantly more often in the RIRM compared with primary metastases of the control group (p = 0.03). It was proved that cystic changes are significantly more common in FNA smears and histological material of RIRM in comparison with primary metastases of experimental and control groups of patients (p &lt;0.05). Conclusions. TThe use of the presence of oxyphilic and cystic changes in the FNA smears and histological material of metastases of the PTC as prognostic factors of RI resistance is proposed. The presence of follicular structures in the materials of primary PTC and metastases can be a prognostic factor of effective RI therapy.

Low urinary iodine is a protective factor of central lymph node metastasis in papillary thyroid cancer: a cross-sectional study

BackgroundAn abrupt increase of thyroid cancer has been witnessed paralleling the supplemented iodine intake in formerly iodine-deficient countries. And increased iodine intake has been linked to the rising incidence rate of papillary thyroid cancer (PTC). However, the correlation between iodine and clinicopathological features of PTC has not been well-characterized. This study aimed to investigate the associations between iodine intake and the clinicopathological features of PTC patients.MethodsThree hundred and fifty-nine PTC patients who received surgical treatment in Peking Union Medical College Hospital from May 2015 to November 2020 were retrospectively reviewed. The associations between urinary iodine (UI), urinary iodine/creatinine ratio (UI/U-Cr), and the clinicopathological features of PTC were analyzed. Univariate and multivariate analysis were performed to investigate the relationship between UI level and central lymph node metastasis (CLNM).ResultsThere were no significant differences in UI in different groups according to the variables studied, except that patients with CLNM had higher UI level than CLNM(−) patients. No associations were found between UI/U-Cr and clinicopathological features except variant subtypes (classic/follicular). After dividing patients into high-iodine group and low-iodine group, more patients were found to have CLNM in the high-iodine group (p = 0.02). In addition, younger age, larger tumor size, and classic variant were positively correlated with CLNM (p < 0.05). Univariate analysis showed that insufficient iodine intake (≤ 99 μg/L) was associated with decreased CLNM risk in PTC. And after defining insufficient iodine intake as ≤ 109 μg/L and above requirements as ≥ 190 μg/L, multivariate analysis showed that lower iodine was associated with CLNM in total population of PTC (OR 0.53, 95% CI 0.31–0.91) and in PTC < 1 cm (papillary thyroid microcarcinoma, PTMC) (OR 0.43, 95% CI 0.21–0.87).ConclusionsLow iodine was a protective factor for CLNM in papillary thyroid cancer, particularly in those < 1 cm. These results indicated that iodine may not only be an initiator of tumorigenesis, but also a promoter of the development of PTC.

Association of BMI with Clinicopathological Features of Papillary Thyroid Cancer: A Systematic Review and Meta-Analysis.

Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer. The incidence of PTC is rising in tandem with an obesity epidemic. Associations have been demonstrated between increased body mass index (BMI) and worse oncological outcomes in a number of malignancies. However, research on this topic in PTC to date has been inconsistent, often due to limited data. This study aimed to measure the association between BMI and potentially adverse clinicopathological features of PTC. A meta-analysis of studies reporting outcomes after surgical treatment of PTC was performed. PubMed, Embase and the Cochrane Library were searched systematically to identify studies which provided data on BMI and clinicopathologic features of PTC. Relevant data were extracted and synthesis performed using adjusted odds ratios where available and crude values when not. Data were analysed by inverse variance using random and fixed effects models. Data on 35,237 patients from 15 studies met the criteria for inclusion. Obesity was associated with larger tumour size (MD = 0.17cm [0.05, 0.29]), increased rates of multifocality (OR = 1.41 [1.16, 1.70]), extrathyroidal extension (OR = 1.70 [1.39, 2.07]) and nodal spread (OR = 1.18 [1.07, 1.30]). Associations were more pronounced as BMI increased. There was no association between BMI and bilaterality, vascular invasion or metastatic spread. Increased BMI is significantly associated with multiple potentially adverse features of PTC. The effect on long-term oncological outcomes requires further evaluation.

Identifying potential metabolic tissue biomarkers for papillary thyroid cancer in different iodine nutrient regions.

To investigate the applicability of metabolomics to select thyroid cancer-associated biomarkers and discover the effects of iodine on metabolic changes in thyroid cancer. In this study, a total of 33 papillary thyroid cancer (PTC) patients from areas with iodine excess and 32 PTC patients from areas with adequate iodine were recruited, and their cancerous tissue and paracancerous tissue were collected. These specimens were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/QTOF/MS) in conjunction with multivariate statistical analysis. Good separations were obtained for PTC tissue vs. paracancerous tissue, and 15 metabolites, including L-octanoylcarnitine, N-arachidonoylglycine, and others were found to be disturbed in PTC tissue. Moreover, the metabolic profile presented considerable separation between PTC tissue from different iodine areas, and 15 metabolomic biomarkers were found to be differentially expressed. Among them, 10 metabolites, including arachidonoylcarnitine and LysoPCs, were related to thyroid cancer and excess iodine. These biomarkers play a role in arachidonic acid metabolism pathways and others. In addition, biomarkers such as 3,5-tetradecadiencarnitine and oxidized glutathione were significantly correlated with thyroid function, and biomarkers such as L-octanoylcarnitine and arachidonic acid were significantly correlated with the clinical characteristics of PTC. Distinct differences in metabolic profiles were found to exist between PTCs from areas with different levels of iodine nutrition. The identified biomarkers have significant potential for diagnosing PTC and investigating its underlying mechanisms.

Associations between essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid cancer.

Aim of this study was to evaluate the association between multiple essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid carcinoma (PTC). The concentrations of 10 essential microelements in urine [cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), strontium (Sr), zinc (Zn), and iodine (I)] were measured in 608 patients newly diagnosed with PTC, including 154 males and 454 females. Chi square test and Wilcoxon rank sum test were used to compare general characteristics among males and females. Multivariate logistic regression was used to evaluate the associations between essential microelements and PTC clinicopathologic characteristics in single- and multi-microelement models. In this study, we only observed that the frequency of lymph node metastasis in males was higher than in females, and males had higher levels of zinc than females, but males had lower levels of iodine than females. It was found that high levels of Fe were associated with decreased risk of PTC tumor size > 1cm, capsular invasion, and advanced T stage (T3/4a/4b). High levels of Co and Mo were associated with decreased risk of capsular invasion and lymph node metastasis, respectively. However, high levels of Mn and Sr were associated with increased risk of capsular invasion and multifocality respectively, and both were associated with increased risk of advanced T stage (T3/4a/4b). These findings indicated that certain essential microelements might have potential effects on PTC progression and aggressiveness. Further studies are required to confirm these findings.

Association Between the Presence of Female-Specific Tumors and Aggressive Clinicopathological Features in Papillary Thyroid Cancer: A Retrospective Analysis of 9,822 Cases

ObjectiveTo investigate the association between the presence of female-specific tumors and aggressive clinicopathological features in papillary thyroid cancer (PTC).MethodsThis study retrospectively analyzed 9,822 female cases between June 2008 and December 2017. Odds ratios and corresponding 95% confidence intervals were calculated. Findings were stratified by age and body mass index (BMI) in different models.Results1443/9822 (14.7%) patients with PTC had a female-specific tumor. Presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter (adjusted OR = 1.446, 95% CI 1.136–1.840, P = 0.003), but a protective factor against extrathyroidal extension of PTC (adjusted OR = 0.650, 95%CI 0.500–0.845, P = 0.001). Presence of a benign uterine mass was an independent risk factor for multifocal PTC (adjusted OR = 1.305, 95%CI 1.113–1.531, P = 0.001). Analyses stratified by age and BMI revealed the presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter in patients aged <36 years (adjusted OR = 1.711, 95% CI 1.063–2.754, P = 0.027), and a protective factor against extrathyroidal extension of PTC in patients aged ≥36 - <42 years (OR adjusted = 0.533, 95% CI 0.302–0.941, P = 0.030) or with a BMI ≥ 23.4 kg/m2 (BMI ≥ 23.4 to < 25.7 kg/m2, adjusted OR = 0.441, 95% CI 0.246–0.792, P = 0.006; BMI ≥25.7 kg/m2, adjusted OR = 0.558, 95% CI 0.315–0.998, P 2 = 0.045). Presence of a benign uterine mass was an independent risk factor for multifocal PTC in patients aged ≥49 years (adjusted OR = 1.397, 95% CI 1.088–1.793, P = 0.009) or with a BMI <21.5 kg/m2 (OR adjusted = 1.745, 95% CI 1.214–2.509, P = 0.003).ConclusionThe presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter and a protective factor against extrathyroidal extension of PTC, while the presence of a benign uterine mass was an independent risk factor for multifocal PTC. Data from this study may help surgeons propose more personalized treatment plans when encountering patients with PTC and female-specific benign tumors.

Ultrasound Echogenicity of Papillary Thyroid Cancer Is Affected by Tumor Growth Patterns and Tumor Fibrosis.

The association between preoperative ultrasound (US) echogenicity and histopathological characteristics of papillary thyroid cancer (PTC) has been rarely investigated is not well characterized. This study evaluated a relationship between the clinical characteristics of PTC, histopathological phenomena including tumor growth patterns (TGPs) and tumor fibrosis (TF), and US echogenicity. In total, 170 patients with PTC (<2 cm) underwent total thyroidectomy with central neck dissection. Demographics, US echogenicity, tumor size, extra-thyroidal extension (ETE), lymph node metastasis (LNM) within the central and lateral neck, TGPs, and TF percentage were reviewed. Patients with TGP II (encapsulated growth with partial pericapsular extension) and III (infiltrative growth) were more frequently burdened by ETE and lateral neck LNM compared to patients with TGP I (encapsulated growth with a well-defined cystic or solid characteristic). Older age was significantly deterministic of TGP III, and male gender and higher TF percentage were independent risk factors for lateral neck LNM. TGP III and TF were independent determining factors for marked hypoechogenicity on US. PTC with TGP II and III and higher tumor fibrosis exhibited more aggressive clinicopathologic behaviors. TGP III and TF were determinants for marked hypoechogenicity.

Positive Thyroid Peroxidase Antibody and Thyroglobulin Antibody are Associated With Better Clinicopathologic Features of Papillary Thyroid Cancer

ObjectiveTo compare the thyroid autoantibody status of patients with papillary thyroid cancer (PTC) and benign nodular goiter as well as possible associations between thyroid autoantibodies and clinicopathologic features of PTC. MethodsA total of 3934 participants who underwent thyroidectomy were enrolled in this retrospective study. Patients were divided into PTC and benign nodule groups according to pathological diagnosis. Based on the preoperative serum antibody results, PTC patients were divided into thyroid peroxidase antibody (TPOAb)-positive, thyroglobulin antibody (TgAb)-positive, dual TPOAb- and TgAb-positive, or antibody-negative groups. ResultsOf the 3934 enrolled patients, 2926 (74.4%) were diagnosed with PTC. Multivariate regression analyses suggested that high thyroid-stimulating hormone levels (adjusted odds ratio [OR] = 1.732, 95% CI [1.485-2.021], P < .001), positive TgAb (adjusted OR = 1.768, 95% CI [1.436-2.178], P < .001), and positive TPOAb (adjusted OR = 1.452, 95% CI [1.148-1.836], P = .002) were independent risk factors for predicting malignancy of thyroid nodules. Multinomial multiple logistic regression analyses indicated that positive TPOAb alone was an independent predictor of less central lymph node metastasis in PTC patients (adjusted OR = 0.643, 95% CI [0.448-0.923], P = .017), whereas positive TgAb alone was significantly associated with less extrathyroidal extension (adjusted OR = 0.778, 95% CI [0.622-0.974], P = .028). PTC patients with dual-positive TPOAb and TgAb displayed a decreased incidence of extrathyroidal extension (adjusted OR = 0.767, 95% CI [0.623-0.944], P = .012) and central lymph node metastasis (adjusted OR = 0.784, 95% CI [0.624-0.986], P = .037). ConclusionAlthough preoperative positive TPOAb and TgAb are independent predictive markers for PTC, they are also associated with better clinicopathologic features of PTC.

Immortalization up-regulated protein promotes tumorigenesis and inhibits apoptosis of papillary thyroid cancer.

The incidence of thyroid cancer is increasing in recent years worldwide, but the underlying mechanisms await further exploration. We utilized the bioinformatic analysis to discover that Immortalization up‐regulated protein (IMUP) could be a potential oncogene in the papillary thyroid cancer (PTC). We verified this finding in several databases and locally validated cohorts. Clinicopathological features analyses showed that high expression of IMUP is positively related to malignant clinicopathological features in PTC. Braf‐like PTC patients with higher IMUP expression had shorter disease‐free survival. The biological function of IMUP in PTC cell lines (KTC‐1 and TPC‐1) was investigated using small interfering RNA. Our results showed that silencing IMUP suppresses proliferation, migration and invasion while inducing apoptosis in PTC cell lines. Changes of the expression of apoptosis‐related molecules were identified by real‐time quantitative polymerase chain reaction and Western blotting. We also found that YAP1 and TAZ, the critical effectors in the Hippo pathway, were down‐regulated when the IMUP is silenced. Rescue experiments showed that overexpression of YAP1 reverses the tumour inhibitory effect caused by IMUP knockdown. Our study demonstrated that IMUP has an oncogenic function in PTC and might be a new target gene in the treatment of PTC.

MON-508 Clinicopathological Features of Papillary Thyroid Cancer After Fukushima and Chernobyl Accidents

The phenomenon of a sharp increase in the incidence of thyroid cancer worldwide is now under debate. Screening activity, diagnostic improvements or real rise in incidence as a result of unknown carcinogens are discussed. Studies in Belarus after Chernobyl showed that the synergistic influence of radiation and nitrates might lead to an increased thyroid cancer (TC) risk in children. For better understanding of the etiology, we compared the published clinical data of pediatric TC patients after the nuclear emergency of Fukushima with the observations we made after the Chernobyl accident.In a large-scale survey after the Fukushima accident, 300,476 subjects were screened and by September 2018, 191 subjects were diagnosed with thyroid malignancy or suspected malignancy by fine needle aspiration. Mean age of TC patients was 17.8 years at presentation. Mean tumor size was 14.9 mm. Postoperative lymph node metastasis, extra-thyroidal invasion, and pulmonary metastasis were detected in 79%, 45%, and 2.1% of all cases, respectively. Only 4.8% TC cases were staged as low risk pT1aN0M0 (Suzuki et al. 2018). For comparison, in Belarus patients mean age was 13.0 years at presentation (1078 cases), mean tumor size 14.4 mm. Lymph node metastases were observed in 74%, pulmonary metastasis in 11% and extra-thyroidal extension in 48.5 - 64.1% (with respect to latency period). The low risk (pT1aN0M0) TC patients were diagnosed in 19.2% cases.The most of TC cases from Japan and Belarus were clinically significant, not “overdiagnosed” and screened on time. Given that the accidental thyroid doses were very low in Japanese cases, it would be very important to evaluate and compare the exposure to endocrine disruptors as e.g. nitrates and low radiation doses from diagnostic procedures (dental X-ray examination and computed tomography).Referece:Suzuki S, Matsumoto Y, Ookouchi C, Nakano K, Iwadate M, Suzuki S, Nakamura I, Fukushima T, Mizunuma H, Yamashita S, Takenoshita S. The clinicopathological features of childhood and adolescent thyroid cancer in Fukushima after the Fukushima Daiichi nuclear power plant accident. Thyroid. 2018; Supplement 1, (Poster 136).

ASO Author Reflections: Characteristics of Papillary Thyroid Cancer of Thyroid Isthmus and Clinical Implications of Its Extrathyroidal Extension.

ASO Author Reflections: Characteristics of Papillary Thyroid Cancer of Thyroid Isthmus and Clinical Implications of Its Extrathyroidal Extension.

Bilateral papillary thyroid cancer in children: Risk factors and frequency of postoperative diagnosis

BackgroundThe recommendation for children with papillary thyroid cancer (PTC) is total thyroidectomy (TT) based on the incidence of bilateral disease. Evaluating this assumption, we reviewed the characteristics of bilateral PTC in a large cohort of children. MethodsA retrospective chart review for patients surgically treated for PTC from 2009 to 2018 analyzing preoperative risk factors, ultrasound findings, and pathology results was performed. Bilateral disease was defined as pathologic PTC in the contralateral lobe, including microscopic disease. ResultsOf the 172 patients included, 38.4% had bilateral disease with 23% diagnosed postoperatively. Multifocal disease on ultrasound was associated with bilateral disease (OR 2.9, 95% CI 1.5–5.9, p = 0.002). Nodule dimension >2 cm was associated with increased risk for postoperative bilateral disease (OR 3.5, 95% CI 1.6–7.4, p = 0.001). Patients with bilateral disease were more likely to have extrathyroidal extension, lymphovascular invasion, positive central lymph nodes, and extranodal extension (p < 0.001 for all). Diffuse-sclerosing variant PTC was also associated with bilateral disease. ConclusionThirty-eight percent of children were diagnosed with PTC demonstrate bilateral disease. Nearly one in four have occult bilateral disease. The features that predicted bilateral disease were multifocality, widely invasive PTC on ultrasound, and the presence of lymphadenopathy. Thus, TT is the appropriate surgical approach for pediatric patients with PTC. Type of StudyClinical Research, Retrospective Review. Level of EvidenceLevel IV.

Suspicious ultrasound and clinicopathological features of papillary thyroid carcinoma predict the status of TERT promoter.

To investigate the value of ultrasound (US) and clinicopathological features of papillary thyroid cancer (PTC) in predicting Telomerase Reverse Transcriptase (TERT) promoter mutations. Preoperative US images of 351 surgically confirmed PTCs were evaluated in terms of PTCs size and US features. The basic clinicopathological features were also retrieved. Univariate and multivariate analyses were performed to identify the risk factors for TERT promoter mutations. A scoring system was developed based on the cumulative number of risk factors. The area under the receiver operating characteristic curve (AUC) and cut-off value were calculated to evaluate the diagnostic performance of the scoring system for predicting TERT promoter mutations. TERT promoter mutations were found in 4.84% (17/351) of patients with PTCs. Patient age >50 years (OR: 6.244, P = 0.006), multifocality (OR: 21.071, P = 0.022), taller-than-wide shape (OR: 4.934, P = 0.029), microlobulated margin (OR: 4786, P = 0.032), and capsule contact or involvement (OR: 4.668, P = 0.030) were independent risk factors for TERT promoter mutations. TERT promoter mutations were relevant to more suspicious US and clinicopathological features than TERT promoter wild-type PTC (median, 4 vs. 1, P < 0.001). The cut-off value was 2.5 and the associated AUC was 0.908 (P < 0.001). The probability of TERT promoter mutations increases along with the suspicious US features and clinicopathological characteristics, which may help to recognize patients who deserve a different approach, in terms of management and follow-up, in view of the worst outcome associated to this mutation.

The effect of TP53 and P21 gene polymorphisms on papillary thyroid carcinoma susceptibility and clinical/pathological features.

Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Genetic polymorphisms of the TP53 and P21 genes are the candidate variants in various cancers development. This study investigated whether the polymorphisms in TP53 (rs1042522) and P21 (rs1059234 and rs1801270) affect the risk of PTC and whether such the genotype of these polymorphisms is associated with pathological and clinical characteristics of PTC. A case-control study was conducted with 286 Iranian people, including 131 PTC cases and 155 healthy controls. The genetic polymorphisms were investigated by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results suggested that TP53-rs1042522 CC genotype was significantly associated with protection against PTC, in the dominant, recessive and allelic models (OR = 0.4, 95%CI: 0.2-0.8, P = .008; OR = 0.5, 95%CI: 0.3-0.9, P = .01; OR = 0.6, 95%CI: 0.4-0.8, P = .002, respectively). The rs1042522 was associated with PTC patients with tumor size greater than 1 cm in dominant and recessive models (OR = 0.2, 95%CI = 0.04-0.9, P = .04 and OR = 0.3, 95%CI = 0.1-0.7, P = .009, respectively) and was associated with vascular invasion in dominant model (OR = 0.3, 95%CI = 0.1-0.7, P = .01). No correlation was identified between P21 rs1059234 and rs1801270 polymorphisms and risk of PTC and pathological and clinical characteristics of PTC. Genetic variations in rs1042522 might alter the PTC risk, which could affect tumor size and cause lower incidence of vascular invasion in PTC cases. This was the first report suggesting that no correlation was found between P21 rs1059234 and rs1801270 polymorphisms and PTC risk. Thus, more studies with a larger population size and different ethnic groups and functional assays are needed to confirm our results.

The relation between BRAFV600E mutation and clinicopathological characteristics of papillary thyroid cancer.

Aim BRAF mutation inhibits many tumour suppressor genes, increases pro-angiogenic molecules and reduces radioactive iodine uptake of tumour in papillary thyroid cancer (PTC), giving it more aggressive clinical characteristics. In this study, we aimed to evaluate the effect of BRAF V600E mutation on the clinicopathological features in patients with PTC. Methods The laboratory and clinical findings of 256 PTC patients who were referred to our clinic between 2007 and 2017 were assessed. Subjects involved in the study were divided into two groups depending on the presence of BRAF V600E mutation. Results BRAF V600E mutation testing gave positive results for 65 (25.4%) out of 256 patients. No significant correlation between BRAF V600E mutation, age and gender was detected. There was no difference between the groups in terms of tumour variant, tumour localization, tumour focality, and perineural invasion. In terms of histopathologic characteristics, presence of tumour capsular invasion (p=0.027), extrathyroidal extension (ETE) (p=0.002), absence of pathologically detected lymphocytic thyroiditis (p=0.006) and radio iodine I-131 treatment (p=0.001) were significantly higher in BRAF V600E (+) patients. During a followup period, four patients with BRAF V600E (+) and two patients with BRAF V600E (-) status underwent lateral neck dissection due to lymph node metastasis (p=0.01). Conclusion The presence of BRAF V600E mutation was proved to be a poor prognostic factor. However, in order to further assess the prognostic effect of BRAF V600E mutation in this group of patients and particularly its effect on mortality, long term followup results must be evaluated.

Correlation between Ultrasound-guided Fine-needle Aspiration Combined with BRAF V600EDetection and Invasive Pathological Features of Papillary Thyroid Cancer

To analyze the potential associations of ultrasound-guided fine-needle aspiration(FNA),BRAF V600E gene mutation detection,and the combination of these two techniques with the clinicopathological features of papillary thyroid cancer(PTC). Methods Patients with PTC confirmed by surgery from April 2016 to July 2017 were included in this study.The relationship between clinicopathological features and BRAF V600E mutation,FNA results,and the combination of them were explored. Results The sensitivity of FNA was 86.3%(227/263)and the mutation rate of BRAF V600E was 85.9%(226/263)in 263 patients with PTC.The mutation rate of papillary thyroid microcarcinoma(PTMC)was 91.1%(153/168)and that of non-PTMC was 76.8%(73/95).A total of 225 patients underwent lymph node dissection.The lymph node metastasis rate was 35.6%(80/225),and it was 23.8%(34/143)in PTMC,56.1%(46/82)in non-PTMC;in addition,9.9%(26/263)of PTC patients had extracapsular invasion.BRAF V600E mutation rate was higher in patients with the following features:aged over 45 years(P=0.043);the tumor was FNA diagnosed as malignant or suspected malignant(P=0.011);the tumor had a maximum diameter of ≤1 cm(P=0.001);and the primary tumor was in stage T1(P=0.039);however,there was no significant difference in BRAF V600E mutation rate among patients with different sex,capsule invasion,or lymph node metastasis.The diagnostic sensitivity of FNA was not statistically different under different clinical and pathological characteristics.The clinicopathologic features of FNA and BRAF V600E double-positive patients were not significantly different from those of other patients. Conclusion FNA-confirmed malignancy,BRAF V600E gene mutation,and their double-positive results are not correlated with the invasive pathological features of PTC,and thus their roles in guiding an extended operation(or not)are limited.

Identification of gene co-expression modules and hub genes associated with lymph node metastasis of papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent histological type among thyroid cancers, and some patients are at a high risk for recurrent disease or even death. Identification for the potential biomarkers of PTC may contribute to early discovery of recurrence and treatment. In The Cancer Genome Atlas (TCGA) database, we obtained the information of RNA sequence data and clinical characteristics of PTC. Weighted gene co-expression network analysis (WGCNA) was performed to construct gene co-expression networks and investigate the relationship between modules and clinical traits. Finally, we constructed 16 co-expression modules in 10,428 genes, and three key modules (darkturquoise, lightyellow, and red) associated with tumor N grade were identified. The results of functional annotation indicated that the darkturquoise module was primarily enriched in the regulation of the extracellular matrix (ECM), collagen metabolism, and cell adhesion, the lightyellow module was primarily enriched in the mitochondrial function regulation and energy synthesis, and the red module was primarily enriched in the process of cell junction, apoptosis, and inflammatory response, suggesting their significant role in the progression of PTC. In addition, the hub genes in the three modules were identified and screened for differentially expressed genes (DEGs). Relapse-free survival analyses found that 11 genes (KCNQ3, MET, FN1, ITGA3, RUNX1, ITGA2, PERP, GCSH, FAAH, NGFRAP1, and HSPA5) may play a pivotal role in PTC relapse. In general, our research revealed the key co-expression modules and identified several prognostic biomarkers, which provides some new insights into the lymph node metastasis of PTC.