Papillary Thyroid Cancer Group Research Articles

Importance and Risk Prediction of ABO Blood Group and Rh Factor in Papillary Thyroid Cancer

Objective: There are limited data in the literature regarding the potentialrelationship between thyroid cancer and ABO blood types and Rh factor.The aim of our study was to investigate whether papillary thyroid cancer(PTC) is associated with blood type.Materials and Methods: The present study included patients who presented to Dicle University Faculty of Medicine between June 2009 andDecember 2020 and were diagnosed with PTC as a result of postoperative(thyroidectomy) histopathological analysis. The control group consisted ofindividuals whose blood type was analyzed at a random blood center.Results: Of the 223 patients diagnosed with PTC, 163 (73.1%) were females and 60 (26.9%) were males. In the comparison of patients based onABO blood types and Rh factor, A Rh positive blood type was found 31%less frequently in the PTC group compared with the control group, and thusit was associated with a lower risk of PTC (OR:0.69; 95% Confidence Interval: 0.50–0.96, p=0.029).Conclusions: In our study, we found A Rh positive blood type to be significantly less frequent among patients with PTC. A Rh positive blood type canbe considered as a protective factor indicating a reduced risk of PTC.

The Role of Preoperative Complete Blood Count Indices in the Distinction of Papillary Thyroid Cancer from Nodular Goiter

Aim: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios (respectively, NLR and PLR) have been associated with poor prognosis in various cancers. This study was conducted to investigate PLR and NLR in patients with papillary thyroid cancer (PTC) and nodular goiter (NG). Materials and Methods: Patients who had undergone thyroidectomy at our center were reviewed and the demographic, clinical and histopathological characteristics of patients with PTC or NG were recorded. Hemogram (complete blood count) results were used to calculate NLR and PLR. Results: The groups were similar with respect to age, gender and thyroiditis characteristics. The NG group was found to have significantly larger gland size compared to the PTC group. NLR and PLR values were similar in the two groups (p>0.05 for both). Conclusion: PLR and NLR appear to be exceedingly similar in PTC and NG, and therefore, they cannot be used to distinguish between PTC and NG. However, it may be valuable to conduct future studies that take into account lesion size when comparing these parameters in thyroid nodules.

TNF-α May Exert Different Antitumor Effects in Response to Radioactive Iodine Therapy in Papillary Thyroid Cancer with/without Autoimmune Thyroiditis.

Simple SummaryRecent evidence shows that autoimmune thyroiditis (AIT) may impair the uptake of radioiodine (131I), altering the success of attempted remnant ablation in papillary thyroid cancer (PTC), but the cause is not clear. Finding the mechanisms that govern immune cells during the 131I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale for these reports. Our study was conducted on female patients admitted for 131I therapy. In the PTC group, 131I therapy modulates the production of cytokines in situ, increasing the antitumor immune response accordingly. On the contrary, in the presence of chronic inflammation due to AIT, 131I therapy amplifies innate immunity, leading to a weaker development of adaptive, specific immunity.Autoimmune thyroiditis (AIT) may impair radioiodine (131I) uptake in papillary thyroid cancer (PTC). Finding the mechanisms that govern immune cells during 131I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale. Our study aimed to evaluate the effects of 131I on anti-thyroglobulin antibodies (TgAb), matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1 and tumor necrosis factor-α (TNF-α) and its receptors TNFR1 and TNFR2, in PTC and PTC + AIT patients. Peripheral blood was collected from 56 female patients with PTC and 32 with PTC + AIT before and 4 days after 131I (3.7 GBq). The serum levels of TgAb, MMP-9, TIMP-1, TNF-α, TNFR1 and TNFR2 were measured by ELISA. The mean radioactivity of blood samples collected after 131I intake was higher in the PTC + AIT group than in PTC (p < 0.001). In the PTC + AIT group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios decreased by 0.38-fold and 0.32-fold after 131I and were positively correlated with the MMP-9/TIMP-1 ratio (r = 0.48, p = 0.005, and r = 0.46, p = 0.007). In the PTC group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios increased by 3.17-fold and 3.33-fold and were negatively correlated with the MMP-9/TIMP-1 ratio (r = −0.62, p < 0.001 and r = −0.58, p < 0.001). Our results demonstrate that TNF-α may exert different antitumor effects in response to 131I therapy depending on the patient’s immune profile.

Multiple lectin assays in detecting glycol-alteration status of serum NRG1 in papillary thyroid cancer.

BackgroundNeuregulin 1 (NRG1) is a membrane glycoprotein mediating cell-to-cell signaling and has a crucial role in the growth and development of various organ systems. Our study explored its diagnostic value in distinguishing BRAF V600E mutant status in papillary thyroid cancer (PTC) patients by analyzing multiple glycan patterns of serum NRG1 through lectin assays.MethodsWe first extracted serum from PTC patients and tested BRAF V600E mutation by immunohistochemical (IHC) staining. Then we applied antibody overlay lectin microarray and lectin blot to detect glycol-alterations of NRG1. Then Aleuria aurantia lectin (AAL) ELISA was performed according to ELISA index to test the protein fucosylation level of NRG1 (Fuc-NRG1).ResultsWe got glycan profiles of 14 lectins, including GNL, GSL2, AAL, BPL, ECL, CAL, NML, HHL, PHA-L, RCA-I, ConA, DBA, PWA and LEL. Six of them, namely, GSL2, BPL, NML, HHL, PHA-L and LEL, had significantly increased binding affinity capacity in BRAF(+) PTC compared with BRAF(-) PTC controls. LEL, BPL and NML tended to bind to NRG1 in BRAF(+) PTC group. Both AAL ELISA and protein ELISA assays showed that the fucosylated structures of NRG1 had a remarkable increase in BRAF V600E mutant PTC patients compared with BRAF wild type PTC controls.ConclusionsThis study sheds a new light on the role of NRG1 glycosylation in PTC. NRG1 could serve as a supplementary glycobiomarker for BRAF indicator in discrimination of PTC patients with BRAF wild type negative fine needle aspiration results.

Increased gene expression of TIMP1 and CHI3L1 in fine-needle aspiration biopsy samples from papillary thyroid cancer as compared to benign nodules.

Thyroid nodules are common ultrasound findings with malignancy rate 7%-15%. Our objective was to assess the relative expression of the tissue inhibitor of metalloproteinase-1 gene (TIMP1) and chitinase-3-like protein 1 gene (CHI3L1) in fine-needle aspiration biopsy (FNAB) washouts and the serum levels of their protein products (TIMP-1 and chitinase-3-like protein 1 known as YKL-40) in patients with papillary thyroid cancer (PTC) and patients with benign nodules. Furthermore, the correlation between gene expression and circulating protein product was evaluated. Eighty patients who underwent FNAB in one tertiary center were recruited in the study. Forty with Bethesda V and VI nodules were operated and PTC was confirmed. The other 40 patients were with Bethesda II nodules. TIMP-1 and YKL-40 serum levels were measured in all subjects. The TIMP1 and CHI3L1 expression was assessed in FNAB washouts from 20 PTC patients and 20 benign cases using quantitative PCR. The relative expression of TIMP1 and CHI3L1 was significantly higher in the PTC group than in the benign group (p < .001 for TIMP1; p=.018 for CHI3L1). The PTC patients had higher serum TIMP-1 than the patients with benign nodules (p=.036). We did not find significant difference in the YKL-40 level between the two groups. TIMP1 and CHI3L1 expression did not correlate with the serum levels of their protein products. FNAB washouts could be used for identification of diagnostic markers. The increased TIMP1 and CHI3L1 expression implies a role of these genes in the PTC carcinogenesis.

Clinicopathological Significance of BRAF (V600E), NRAS (Q61K) and TERT (C228T, C250T and SNP Rs2853669) Mutations in Bulgarian Papillary Thyroid Carcinoma Patients

Abstract Introduction: Thyroid carcinoma is the most common endocrine cancer. Some somatic mutations in genes (BRAF, NRAS and TERT) involved in key signaling pathways and genome stability have been recently identified to play an important role in its development. Very little research has been done on their frequency and clinical relevance in Bulgarian patients with papillary thyroid cancer (PTC). This study is focused on investigating somatic mutation frequency in Bulgarian patients with PTC and their association with clinicopathologic features. Material and Methods: The study included 50 PTC from Bulgarian patients analyzed for mutations in BRAF (V600E), NRAS (Q61K), single nucleotide polymorphism (SNP) rs2853669 and TERT (C228T and C250T) genes by Sanger sequencing. The results were interpreted using Benchling and SeqScape software, and statistical analysis performed with SPSS. Results: In the studied PTC group BRAF(V600E) and TERT (C228T) mutations were found with frequency of 24% and 2%, respectively. Co-occurrence of both mutations was found in 1 patient (2%). The mutations Q61K (NRAS), and C250T (TERT) were not detected. The SNP rs2853669 was found in 18 patients (52.9%). Correlation analysis with the clinical characteristics of the patients revealed statistically significant association with larger size of the tumor for BRAF(V600E) and smaller tumor size for rs2853669. Conclusion: In the present pilot study, we found that BRAF(V600E) and rs2853669 in TERT are common among PCT patients. While the presence of BRAF V600E mutation was associated with large tumors, the presence of rs2853669 in TERT was found in the majority of PCT below 2 cm. More extensive molecular genetic analysis of TERT, BRAF or RAS mutations in larger sample is needed to further elucidate the clinically important diagnostic and prognostic biomarkers for thyroid cancer.

Abnormal Brain Glucose Metabolism in Papillary Thyroid Cancer Patients 4 Weeks After Withdrawal of Levothyroxine: A Cross-Sectional Study Using 18F-FDG PET/CT.

BackgroundThere is no doubt that thyroid dysfunction is associated with psychiatric disorders. A large amount of thyroid carcinoma patients displayed mood disorders after the withdrawal of levothyroxine (LT4). However, it is unclear whether the disorders are related to the transient withdrawal of LT4, and if yes, what the possible underlying mechanism is. This study aims to investigate the abnormal regional cerebral glucose metabolism (rCMRglu) in a group of papillary thyroid cancer (PTC) patients without LT4 for 4 weeks and prove the relationship between the abnormal rCMRglu with depression and anxiety.MethodsBrain 18F-FDG PET/CT data of 38 consecutive PTC patients with high/intermediate-risk from June 2016 to December 2017 have been analyzed. Of the 38 patients, 23 are in the LT4 withdrawal group (WG) and 15 in the LT4 replacement group (RG). These patients were also evaluated for depressive and anxiety symptoms within 24 h after the scans based on the Hamilton Depression Rating Scale (17 items, HRDS-17) and the Hamilton Anxiety Rating Scale (HAMA) respectively.ResultsThirty-eight patients (12 men, 26 women; age range, 25–69 years; mean age, 45.8 years) were selected in the study. Compared with the RG, patients in WG showed depression and anxiety with higher total scores of HRDS-17 and HAMA (14.7 ± 5.8 vs 3.8 ± 5.5, t = −5.74, p = 0.00; 9.3 ± 4.3 vs 2.7 ± 4.1, t = −4.74, p = 0.00, respectively). In the brain glucose metabolism analysis, the WG patients showed lower rCMRglu in Occipital_Mid_R and Postcentral_L. On the other hand, data illustrated significant rCMRglu increases in the Frontal_Sup_Orb_L. Compared with the healthy group (HG), the rCMRglu of the Postcentral_L and Precuneus_L showed hypoactivity, but the Hippocampus_R and the Temporal_Inf_L showed hyperactivity. This analysis yielded a significant correlation between abnormal rCMRglu with the free thyroxine level, the serum thyroid-stimulating hormone level, HRDS-17, and HAMA scores.ConclusionsThe findings showed that more PTC patients exhibited depression and anxiety after LT4 withdrawal for 4 weeks. More attention should be paid to these hypothyroid patients while they were in the hospital. Such a short-term LT4 withdrawal also likely induced abnormal rCMRglu. Our study attempts to explain the possible mechanism of mood disorders related to transient hypothyroidism.

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.

Role of Age at Diagnosis in Defining Potential Familial Nonmedullary Thyroid Cancer in Kindreds With Two Affected Members.

The definition of familial nonmedullary thyroid cancer (FNMTC) in 2 or more first-degree relatives is controversial due to the high probability of observing a sporadic association when only 2 members of first-degree relatives are affected. To evaluate the role of age at diagnosis in differentiating the true cases of FNMTC. From a group of 721 papillary thyroid cancer (PTC) patients, 95 familial PTC (FPTC) patients with 2 first-degree relatives have been identified. They were split in 2 groups: Group 1 consisted of both the proband and the affected relative, with age at diagnosis ≤ 45 years; Group 2 consisted of proband and/or the affected family member, with age at diagnosis > 45 years. The clinical-pathological features and outcome of both FPTC groups were compared with 626 sporadic PTC patients (SPTC). Familial PTC patients with age at diagnosis ≤ 45 years, compared with the matched group of sporadic PTCs, had a more frequent multifocal, bilateral, and extrathyroidal extension of tumor and showed worse outcome. No differences were found between FPTC and SPTC patients with age > 45 years. At multivariate analysis, distant metastases, American Thyroid Association (ATA) risk, and FPTC ≤ 45 years were independent predictors of outcome. Based on the observation that PTC is more aggressive when the diagnosis is made in 2 family members, both with age < 45years, we suggest that the definition of FPTC in kindreds with 2 affected members should also take into account the age at diagnosis as a key element of familial cancer.

Association of Hyperparathyroidism and Papillary Thyroid Cancer: A Multicenter Retrospective Study.

BackgroundConcomitant papillary thyroid cancer (PTC) and hyperparathyroidism (HPT) have been reported in several studies. Our study aimed to investigate the incidence of concomitant PTC in HPT patients upon preoperative diagnosis and present a clinical opinion on detecting thyroid malignancy in case of parathyroidectomy.MethodsPatients who underwent parathyroidectomy between January 2009 and December 2019 in two medical centers were included. Of the 279 participants 154 were diagnosed as primary hyperparathyroidism (pHPT) and 125 as secondary hyperparathyroidism (sHPT). The incidence of concomitant PTC and its clinical characteristics were compared with 98 patients who underwent thyroidectomy and were diagnosed with classical PTC during the same period.ResultsConcurrent PTC was detected in 14 patients (9.1%) with pHPT and in nine patients (7.2%) with sHPT. Ten (71.4%) and seven (77.8%) PTCs were microcarcinomas in the pHPT and sHPT cases respectively. In the pHPT patients, vitamin D was lower in the pHPT+PTC group (13.0±3.7 ng/mL) than in the pHPT-only group (18.5±10.4 ng/mL; P=0.01). Vitamin D levels were also lower in the sHPT+PTC group (12.3±5.6 ng/mL) than in the sHPT-only group (18.0±10.2 ng/mL; P=0.12). In the concomitant PTC group, lymph node ratio was higher than in the classical PTC group (P=0.00).ConclusionA high prevalence of concomitant PTC was seen in patients with pHPT and sHPT. Those concomitant PTCs were mostly microcarcinomas and had more aggressive features, suggesting that efforts should be made to detect concomitant malignancies in the preoperative parathyroidectomy evaluation.

Effects of the MTOR and AKT1 genes polymorphisms on papillary thyroid cancer development

Papillary thyroid cancer (PTC) is the most common form of thyroid cancer, comprising 80% of all thyroid malignancies. The phosphoinositide-3-kinase-protein kinase B/Akt (PI3K-PKB/Akt) pathway is a main pathway in control of cell growth. Activated mTOR and Akt are involved in the development and progression of the PTC. This study aimed to evaluate the effects of MTOR (rs2536 and rs2295080) and AKT1 (rs2494732, rs1130214, and rs1130233) polymorphisms on PTC susceptibility. This study was conducted on 131 PTC patients and 144 healthy subjects. Genotype analysis was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Our results showed no statistically significant association between MTOR rs2536, AKT1 rs2494732, and rs1130214 polymorphisms and PTC development. However, MTOR rs2295080 polymorphism was found to be associated with a decreased risk of PTC in dominant and allelic models. The TT genotype of AKT1 rs1130233 was significantly higher in the PTC group in comparison to the controls, with a 3.5-fold increased risk for developing PTC. Furthermore, the allelic distribution also showed the T allele of rs1130233 as a risk factor for PTC occurrence. In conclusion, our results suggest the MTOR rs2295080 and AkT1 rs1130233 as the protective and risk factors for PTC development, respectively.

Potential role of iodine excess in papillary thyroid cancer and benign thyroid tumor: A case-control study.

The relationship between nutritional status of iodine and thyroid tumor is unclear. We investigated the association between urinary iodine concentration and thyroid function in patients with papillary thyroid cancer, benign thyroid tumor and healthy individuals. We compared the biomarkers of thyroid function and urinary iodine concentration within and between each group. A regression analysis was used to identify risk factors for papillary thyroid cancer. Correlation analysis was performed to determine whether any significant correlation exists between urinary iodine concentration and thyroid function biomarkers. The iodine nutrition statuses of these three groups were adequate (median urinary iodine concentration= 100-199 μg/L). However, the median urinary iodine concentration of papillary thyroid cancer (174.7 μg/L) and benign thyroid tumor (165.04 μg/L) groups was significantly higher than that of the healthy control group (135.8 μg/L) (p<0.05). The regression analysis showed that thyroglobulin antibody was an independent risk factor for papillary thyroid cancer. After adjusting for age and gender, the association between thyroglobulin antibody and urinary iodine concentration was significant (β: 0.002; p<0.05). In subgroup analyses, significant correlations was noted only in the papillary thyroid cancer group (adjusted β: 0.002; 95% confidence interval: 0.000- 0.003). Excessive iodine in patients with thyroid tumors may affect thyroglobulin antibody, which may be an independent risk factor for papillary thyroid cancer.

Isthmic Papillary Thyroid Carcinoma Presents a Unique Pattern of Central Lymph Node Metastasis.

PurposeTreatment protocols for occult central lymph node metastasis (LNM) associated with papillary thyroid cancer (PTC) located in the isthmus are debatable. We aimed to analyze the pattern of occult central LNM in isthmic PTC, including risk factors for bilateral paratracheal LNM.Patients and MethodsConsecutive patients with PTC were recruited to this study. All patients underwent total thyroidectomy and prophylactic bilateral central neck dissection. The clinicopathologic features and distribution of central LNM were compared between the two groups, and risk factors for bilateral paratracheal LNM were analyzed.ResultsA total of 174 patients with PTC were enrolled in this study, of whom 87 patients had isthmic PTC (study group) and 87 patients had lobe-originating PTC (control group). The two groups had comparable demographics and tumor features. There were higher frequencies of pretracheal LNM (P =0.001) and bilateral paratracheal LNM (P = 0.002) in the isthmic PTC group. Bilateral paratracheal LNM was significantly associated with age <55 years (P = 0.037), capsular invasion (P = 0.034), tumor location (isthmus) (P < 0.001), BRAF gene mutation (P = 0.013), and pretracheal LNM (P < 0.001). Isthmus location (odds ratio [OR]: 4.116, 95% confidence interval [CI]: 1.264–13.433, P = 0.019) and pretracheal LNM (OR: 3.422, 95% CI: 1.214–9.642, P = 0.020) were independent risk factors for bilateral paratracheal LNM.ConclusionBecause of its unique anatomic location, isthmic PTC differs from PTC in the lobe with respect to pretracheal and bilateral paratracheal LNM, even in patients of comparable age, sex, tumor size, extrathyroidal extension, BRAF mutation, and pathologic TNM staging. The isthmus location was found to be an independent risk factor for bilateral paratracheal LNM. This information may contribute to the development of an appropriate surgical protocol for isthmic PTC.

Association between TSHR gene methylation and papillary thyroid cancer: a meta-analysis.

To explore the association between the thyroid stimulating hormone receptor (TSHR) gene methylation and human papillary thyroid cancer (PTC), as well as PTC related clinicopathological indicators. We searched PubMed, Embase, Medline, and Web of Science databases through computer for articles published in English on association between methylation of TSHR gene and PTC. Articles published in Chinese were searched in China National Knowledge Infrastructure (CNKI), WanFang, China Biology Medicine (CBM) disc, and WeiPu databases. Database search took place in the 4th week of October. Totally 914 samples from 14 case-control studies were included in our meta-analysis. The methylation rate of TSHR gene in PTC group was significantly greater than that in control group (OR = 6.45, 95% CI 3.03, 13.71, P < 0.001). The subgroup analysis results showed the incidence of TSHR gene methylation was higher in autologous controls (OR = 16.39, 95% CI 8.83, 30.42, P < 0.001), Asian races (OR = 8.26, 95% CI 3.54, 19.23, P < 0.001), and Chinese (OR = 11.40, 95% CI 5.56, 23.39, P < 0.001). Hierarchical analysis of PTC related clinicopathological indicators showed that TSHR gene methylation rate are higher in PTC patients over 45 years (OR = 1.65, 95% CI 1.07, 2.55, P < 0.05) and lymph node metastasis (OR = 5.36, 95% CI 1.54, 18.67, P < 0.01). In addition, the occurrence of TSHR gene methylation had also been shown to be related to the clinical stage (OR = 0.23, 95% CI 0.07, 0.70, P < 0.05) and size (OR = 0.19, 95% CI 0.11, 0.32, P < 0.01) of tumors. The result of sensitivity analysis showed the combined results of the studies included in the meta-analysis were fairly stable. Begg's and Egger's tests also suggested that there was no significance publication bias (P > 0.1). The rate of TSHR gene methylation is higher in PTC and it may be associated with the pathogenesis of human PTC, suggesting that TSHR gene may be a candidate marker for PTC diagnosis. In addition, the occurrence of TSHR gene methylation in PTC patients is closely related to age, lymph node metastasis, clinical stage, and tumor size, suggesting that TSHR gene may be used as an index to judge the severity of PTC.

Prognostic significance of the sum of the diameters of single foci in multifocal papillary thyroid cancer: the concept of new-old tumor burden.

Aim:The prognostic value of multifocality (Mu) in papillary thyroid cancer (PTC) remains controversial. The present study aimed to investigate this issue and test the possible prognostic significance of the sum of the diameters of single foci (SDSF), the total number of foci (TNF), and primary tumor size (PTS) in multifocal PTC.Methods:We retrospectively analyzed a single-center consecutive series of 370 PTCs. For multifocal cases we analyzed bilaterality occurrence, SDSF, TNF, and PTS.Results:Mu was observed in 41.1% PTCs, and bilaterality in 30%. Mu was associated with an advanced T-category. In bilateral multifocal PTC, the PTS was larger, and microPTC was less frequent, while T-categories were higher. Mu and bilaterality per se had no impact on prognosis. At univariate analysis, PTS, SDSF, vascular invasion, lymph node metastases, distant metastases, T-categories, Initial Risk Stratification System score, second treatment and TERT promoter mutation correlated with persistence/recurrence or death in the multifocal PTC group. On multivariate Cox proportional hazards regression analyses, SDSF again independently predicted persistence/recurrence or death in multifocal PTCs. We found that a cut-off for SDSF less than 40 mm was able to identify multifocal PTC patients with a very low risk of persistence/recurrence (negative predictive value 96.9%). Disease-free survival was significantly shorter in patients with multifocal PTCs and SDSF ⩾40 mm.Conclusions:Mu and bilaterality per se were not prognostically significant. SDSF emerged as a new independent prognostic factor for persistence/recurrence of multifocal PTC. SDSF might better represent the tumor burden in multifocal PTC, with SDSF < 40 mm identifying multifocal PTC patients with a good prognosis.

Short Call Abstracts

Short Call Abstracts

Altered Serum MicroRNA Profile May Serve as an Auxiliary Tool for Discriminating Aggressive Thyroid Carcinoma from Nonaggressive Thyroid Cancer and Benign Thyroid Nodules.

Thyroid cancers are the most common malignancy of the endocrine system; however, there is no reliable blood biomarkers for thyroid cancer diagnosis and even for aggressive and nonaggressive thyroid cancers as well as benign nodule discrimination. The present study is aimed at evaluating whether circulating microRNA (miRNA) can differentiate aggressive and nonaggressive thyroid cancer from benign thyroid nodules. In this study, we performed a multiphase, case-control study to screen serum miRNA expression profile in 100 patients with papillary thyroid cancer (PTC), 15 patients with aggressive medullary thyroid carcinoma (MTC), 91 patients with benign nodules, and 89 healthy controls using TaqMan low-density array followed by extensive reverse transcription quantitative real-time PCR validation. The results showed that the serum levels of miR-222-3p, miR-17-5p, and miR-451a were markedly increased, while miR-146a-5p, miR-132-3p, and miR-183-3p were significantly decreased in the PTC and benign nodule groups compared with the control group. There was no difference in the miRNA expression profile between the PTC group and the benign nodule group. Nevertheless, the serum levels of miR-222-3p and miR-17-5p were significantly increased in the MTC group than the benign nodule and control group. Moreover, receiver operating characteristic curve analyses demonstrated that the 2 miRNAs and their panel can accurately discriminate MTC from the benign nodule group and healthy controls. These findings indicated that the altered circulating miRNAs may discriminate PTC and benign thyroid nodules from controls, and serum miR-222-3p and miR-17-5p have the potential to serve as auxiliary tools for diagnosing more aggressive thyroid carcinomas, such as MTC.

Thyroglobulin antibody is associated with elevated risk of papillary thyroid cancer among female patients

Objective To determine the correlation between papillary thyroid cancer(PTC) malignancy with thyroid antibody expression level. Methods In this retrospective study, 4 046 goiter patients with complete clinical data who have undergone thyroidectomy were separated into the benign nodule (n=1 357) and PTC groups (n=2 689), and their preoperative thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) were assessed through antibody analysis. HT was determined based on the postoperative histopathology. The collected data were then evaluated for the correlation with PTC malignancy through statistical tests. Results In general, patients in the PTC group showed a significantly higher TgAb positivity (10.9%) than those in the benign group (5.6%, P<0.01). Among female patients, a higher TgAb positivity was observed for those in the PTC group than those in the benign group (14.0% vs 7.0%, P<0.01), while no significant difference between groups was observed in male patients. The high odds ratio of 2.18 supports the significant correlation between TgAb-positive status and higher risk of developing PTC in women (P<0.05). However, the risk of developing PTC was not correlated with higher TgAb titre. TgAb was not significantly correlated with the mass size, multifocality, lymph node metastasis or the TNM classification of malignant tumor stage Ⅲ/Ⅳ. Conclusion The increasing risk of PTC is related to TgAb among female patients, but it will not increase as TgAb titer rises. It is not associated with PTC aggressiveness. Key words: Thyroid antibodies; Papillary thyroid cancer; Gender differences

Does Primary Hyperparathyroidism Have an Association with Thyroid Papillary Cancer? A Retrospective Cohort Study.

To investigate the relationship between primary hyperparathyroidism (pHPT) and papillary thyroid cancer (PTC). The perioperative findings of 275 patients with pHPT who underwent surgery between January 2014 and December 2017 were retrospectively reviewed. Thirty-one patients were diagnosed with pHPT and PTC concurrently. Pathology results and demographic findings of these patients were compared with 186 patients who underwent thyroidectomy and diagnosed with PTC at the same time interval. The co-occurrence of pHPT and PTC was 11.3% (31/275). The median ages of the pHPT, pHPT + PTC, and PTC groups were 55, 57, and 50years old, respectively (p < 0.001). The diameter of tumor was smaller in the pHPT + PTC group [median 7mm (range 0.5-25mm) vs. 15mm (range 1-100mm)], with higher rates of microcarcinomas (p < 0.001), than the patients in the PTC group. Examination of tumor morphology showed higher rates of tumor capsule invasion and multicentricity in the pHPT + PTC group than those in the isolated PTC group (p = 0.02, p = 0.04, respectively). The pHPT + PTC group had significantly smaller tumor diameter than the PTC group. This result may support the idea that pHPT leads to overdiagnosis of PTC. However, observation of high rates of tumor capsule invasion and multicentricity in the pHPT + PTC group may suggest an associative etiology with more aggressive PTC.

Hyperinsulinemia and thyroid peroxidase antibody in Chinese patients with papillary thyroid cancer.

This study aimed to investigate if hyperinsulinemia and/or insulin resistance was correlated with the occurrence of papillary thyroid cancer (PTC) in a group of Chinese patients. 258 inpatients were included in the study. According to the postoperative pathology results, all subjects were divided into PTC (n = 153) and control groups (with benign thyroid nodules, n = 105). Body mass index (BMI), fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), thyroid-stimulating hormone (TSH), FT4, FT3, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), serum uric acid (UA), and lipid levels. Fasting insulin levels, HOMA-IR values, TPOAb levels, serum TSH levels, and serum uric acid levels in the PTC group were higher than those in the control group (p < 0.05). However, no significant differences in age, gender, BMI, history of hypertension, and the levels of fasting plasma glucose, FT3, FT4, TGAb, total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were observed between the two groups (p > 0.05). After the multiple logistic regression analysis, the occurrence of PTC was positively associated with fasting insulin (odds ratio [OR] = 1.048, 95% confidence interval [CI]: 1.003-1.096, p = 0.037) and TPOAb levels (OR = 1.001, 95% CI: 1.000-1.002, p = 0.032). Moreover, TPOAb level was positively correlated with vague margin (r = 0.126, p = 0.045) and negatively correlated with homogeneous echo (r = -0.179, p = 0.004). However, fasting insulin levels were not correlated with pathological characteristics of PTC. Hyperinsulinemia and higher TPOAb levels might be the risk factors of PTC, but not disease severity in Chinese patients.