Cases Of Papillary Thyroid Carcinoma Research Articles

The prognostic value of the lymphocyte-to-monocyte ratio for high-risk papillary thyroid carcinoma.

Background and AimsThe prognosis of papillary thyroid carcinoma (PTC) is highly variable, even for high-risk cases. The predictive and prognostic role of the lymphocyte-to-monocyte ratio (LMR) has been reported in other cancers. The aim of our present study was to explore the value of LMR prognostic prediction in high-risk PTC patients.Patients and MethodsTwo hundred and twenty-four PTC high-risk cases at West China Hospital were randomized into a training set (112 cases) and testing set (112 cases), while 48 cases in Shang Jin Nan Fu Hospital were included as the external validation set.ResultsA lower preoperative LMR correlated with larger tumor size, advanced N and M stages, and an increased number of multiple PTC cases in the training, testing, and validation sets (all P<0.05 in the three sets). Patients with a high LMR exhibited significantly improved overall and PTC-free survival compared with those of patients with a low LMR in the training, testing, validation, and combined sets (all P<0.05 in the individual and combined sets). Moreover, multivariate analyses identified the LMR as an independent prognostic factor for overall and PTC-free survival. The nomograms for predicting the 5-year mortality and PTC recurrence were developed based on the risk factors in the training set and validated in the independent testing and validation sets.ConclusionThe preoperative LMR was identified as an independent prognostic factor that could be incorporated into the two nomograms with other risk factors to predict overall survival and PTC-free survival for individual patients.

The value of preoperative clinical and sonographic characteristics of clinically node-negative papillary thyroid carcinomain predicting central lymph node metastasis

Objective To investigate the association of preoperative clinical and sonographic characteristics of clinically node-negative (cN0) papillary thyroid carcinoma (PTC) with central lymph node metastasis (CLNM). Methods A total of 514 patients with PTC confirmed by pathology in our hospital were included in the retrospective analysis. Clinical and sonographic characteristics were assessed including age, gender, tumor size, and the distance between the tumor and the capsule. These cases were all diagnosed as cN0 according to clinical and sonography examinations. And the cases were divided into CLNM(+ ) group and CLNM(-) group based on the pathological results. Then statistical analysis was used to evaluate the correlation between CLNM and risk factors of cN0 PTCs. Results ①Of the 514 cN0 PTC cases, 211 cases (41.1%) were CLNM (+ ) and 303 cases (58.9%) were CLNM (-). ②With the presence of capsule invasion in the ultrasound examination, the probability of CLNM(+ ) group was higher than that of CLNM(-) group (62.1% vs 37.9%). ③In the 364 cases without capsule invasion, the probability of CLNM (+ ) was significantly increased when the distance between the tumor and the capsule was <1.5 mm (88.8% vs 11.2%). ④Multivariate analysis showed that risk factors independently associated with CLNM included age <45 years old, tumor maximum diameter ≥10 mm, and the distance between the tumor and the capsule <1.5 mm, among which the distance between the tumor and the capsule <1.5 mm had the highest OR value. Conclusions In cN0 PTC patients, CLNM is associated with age, size and the distance between the tumor and the capsule. Key words: Ultrasonography; Papillary thyroid carcinoma; Central lymph node metastasis

Long-term outcome of rare oncocytic papillary (Hürthle cell) thyroid carcinoma following (adjuvant) initial radioiodine therapy.

Oncocytic (Hürthle cell) papillary thyroid carcinoma (OPTC) is a rare variant of the papillary thyroid carcinoma (PTC) which comprises approximately 1 to 11% of PTC cases. Its clinical course and prognosis have not been comprehensively documented and the clinical outcome remains a controversial issue. Therefore, we investigated the long-term prognosis after thyroidectomy and (adjuvant) initial radioactive iodine therapy (RIT) of OPTC compared to PTC. A total of 563 patients (47 with OPTC and 516 with PTC) with a median follow-up of 9.9 (0.3; 23.5) years were studied. All patients underwent thyroidectomy followed by (adjuvant) initial RIT. Data on the patients' demographics, pathology, laboratory findings, imaging studies, treatment, and follow-up including recurrence, and disease-specific survival were collected. Cox's multivariate regression model was used to identify independent prognostic factors for survival. OPTC patients were significantly older (55.2 ± 12.3years) than PTC patients (50.3 ± 13.5) at the time of initial diagnosis (p value 0.016). Initial tumor size was larger in the OPTC group (2.8 ± 1.8cm for OPTC patients, 1.5 ± 1.2cm for PTC patients, p value < 0.001). Before matching, OPTC patients presented more often with evidence of disease at the last visit of follow-up (p value 0.046). However, this difference was not observed anymore after matching for risk factors (p value 0.637). Disease-specific survival did not differ significantly. Age (HR, 1.183; 95% CI, 1.097-1.276) was identified as an independent prognostic factor for disease-specific survival. OPTC patients predominantly showed a recurrence of distant metastasis within a shorter time despite being not statistically significant. At initial diagnosis, OPTC shows significant differences in terms of age and initial tumor size compared to PTC. Patients suffering from OPTC present with the same clinical long-term outcome indifferent to PTC after (adjuvant) initial RIT after matching.

Immunohistochemical Analysis of Cancer Stem Cell Marker Expression in Papillary Thyroid Cancer.

Cancer stem cell (CSC) markers have prognostic significance in various cancers, but their clinical significance in papillary thyroid carcinoma (PTC) has not been demonstrated. In this study, CSC markers expressed in PTC and their relationships with prognosis were evaluated. We constructed tissue microarrays for 386 PTC cases, divided it into 42 low risk cases and 344 intermediate risk cases according to the American Thyroid Association 2009 Risk Stratification System. Immunohistochemical staining of CSC markers (CD15, CD24, CD44, CD166, and ALDH1A1) was performed, and the proportion of stained cells and immunostaining intensity were evaluated to determine positive marker expression. The relationships between CSC marker expression and other clinicopathological parameters or survival were analyzed. CD15 expression was higher in PTC with intermediate risk than in PTC with low risk (29.4 vs. 11.9%, p = 0.017). According to a multivariate analysis, CD15, CD44, CD166, and ALDH1A1 positivity were independently associated with a shorter progression-free survival (PFS) (odds ratio [OR]: 1.929, 2.960, 7.485, and 3.736; p = 0.016, p = 0.026, p < 0.001, and p = 0.006, respectively). Higher N and cancer stage were the only other clinical factors associated with a shorter PFS (OR: 2.953 and 1.898, p = 0.011 and p = 0.034). Overexpression of CSC markers in PTC was associated with shorter PFS during follow-up. Immunohistochemical staining of CSC markers may provide useful information for predicting patient outcomes.

Coexistent papillary thyroid carcinoma diagnosed in surgically treated patients for primary versus secondary hyperparathyroidism: same incidence, different characteristics

BackgroundThe coexistence of hyperparathyroidism and thyroid cancer presents important diagnostic and management challenges. With minimally invasive parathyroid surgery trending, preoperative thyroid imaging becomes more important as concomitant thyroid and parathyroid lesions are reported. The aim of the study was to evaluate the rate of thyroid cancer in patients operated for either primary (PHPT) or secondary hyperparathyroidism (SHPT).MethodsOur retrospective study included PHPT and SHPT patients submitted to parathyroidectomy and, when indicated, concomitant thyroid surgery between 2010 and 2017.ResultsParathyroidectomy was performed in 217 patients: 140 (64.5%) for PHPT and 77 (35.5%) for SHPT. Concomitant thyroid surgery was performed in 75 patients with PHPT (53.6%), and 19 papillary thyroid carcinomas (PTC) were found, accounting for 13.6% from all cases with PHPT and 25.3% from PHPT cases with concomitant thyroid surgery. Thirty-one of operated SHPT patients (40.3%) also underwent thyroid surgery and 9 PTC cases were diagnosed (11.7% of all SHPT patients and 29% of patients with concomitant thyroid surgery).We found differences between PHPT and SHPT patients (p < 0.001) with respect to age (54.6 ± 13y versus 48.8 ± 12y), female-to-male ratio (8:1 versus ~ 1:1), surgical technique (single gland parathyroidectomy in 82.8% PHPT cases; versus subtotal parathyroidectomy in 85.7% SHPT cases) and presurgical PTH (357.51 ± 38.11 pg/ml versus 1020 ± 161.38 pg/ml).Morphopathological particularities, TNM classification and multifocality incidence of PTC were similar in the two groups. All PTC from patients with SHPT were thyroid microcarcinomas (TMC, i.e. tumors with a diameter smaller than 1 cm), whereas seven out of the 19 cases with PTC and PHPT were larger than 1 cm.ConclusionsPTC was frequently and similarly associated with both PHPT and SHPT irrespective of presurgical PTH levels. Thyroid tumors above 1 cm were found only in patients with PHPT. Investigators should focus also on associated thyroid nodular pathology in patients with PHPT.

Evaluating pre- and post-operation plasma miRNAs of papillary thyroid carcinoma (PTC) patients in comparison to benign nodules

BackgroundThyroid cancer is the most common endocrinology cancer that its incidence has increased in recent decades. miRNAs are new biomarkers in recent studies in the diagnosis and follow-up of these patients.MethodsBlood and thyroid tissue samples were obtained from two groups of included patients (PTC and benign nodules), pre- and post-operation. miRNAs were extracted from these plasma samples and were measured quantitatively. After cDNA synthesis, qPCR was carried out. Then tissue samples were investigated, and their relation to miR expression was studied. These results were analyzed by paired- and independent samples t-test, and non-parametric tests.ResultsmiR-222 and miR-181a declined in PTC patients before and after surgery, significantly (P < 0.001 for both groups), with no significant difference in control group before and after surgery (P = 0.61 for miR-222 and P = 0.06 for miR-181a). The difference between the two groups, pre-and post-operation, was statistically significant (P = 0.01 for miR-222 and P < 0.001 for miR-181a). Comparing case and control groups, pre- and post-operatively, yielded no significant difference, in miR-155-5p levels (P = 0.61 and P = 0.53, respectively). Comparing PTC and control groups before surgery showed a significant difference (P = 0.01), while no significant difference was observed comparing them after surgery, in miR146-a (P = 0.27). Our results depicted a higher miR-155-5p and miR-146a expression before surgery than after it (P < 0.001 in both groups, for both miRs). We found a significant relationship between miR-222 and BRAFV600E mutation and significantly higher levels of miR-181a with increasing tumor size in PTC patients.ConclusionmiR-222 showed overexpression in all PTC cases, which is indicative of a relation between miRNA and PTC. Also, comparing miR-181 and miR-146a showed a significant difference between cancerous and benign cases. miR-155-5p as an inflammatory factor, showed no significant changes, comparing two groups.

Reactive C cell hyperplasia as an incidental finding after thyroidectomy for papillary carcinoma.

The biologic and clinical significance of reactive C cell hyperplasia (CCH), adjacent to differentiated thyroid cancers, remains unknown. Our aim was to investigate the presence of CCH in thyroidectomy specimens with papillary thyroid carcinomas (PTC) and discuss its epidemiology and histology. In total, 413 patients were prospectively included in the study (189 benign goiters, 224 PTC). Reactive CCH was observed in 9.8% of PTC cases (32% males, 68% females, mean age 48.3 ± 16.4years) and usually ipsilateral to the primary tumor (91%). Histologically, CCH was either focal (91%) or diffuse (9%) and almost always (92%) found in the middle or upper thirds of the thyroid lobes. Patients with PTC/CCH were generally younger than patients with benign goiters (0.027). On the other hand, patients with PTC and with PTC/CCH did not differ in terms of age, gender, basal calcitonin levels, primary tumor size, multifocality, extrathyroidal invasion, or lymph node metastasis. Thyroiditis, however, was more frequent in cases with PTC/CCH compared to PTC alone. Reactive CCH is considered a physiological response of the C cells to various stimuli, differentiated thyroid cancer among others. It bears no malignant potential and requires no additional treatment, following thyroidectomy.

Prognostic significance of DNMT3A alterations in Middle Eastern papillary thyroid carcinoma

BackgroundThyroid cancer is the second most common cancer affecting Saudi women after breast cancer, with papillary thyroid carcinoma (PTC) accounting for 80–90% of thyroid cancers. DNA methyltransferases affect DNA methylation, and it is thought that they play an important role in the malignant transformation of various cancers. MethodsWe sought to evaluate the frequency of DNA methyltransferase 3A (DNMT3A) alterations in a large cohort of >1000 PTC cases using exome sequencing, capture sequencing, immunohistochemistry and methylation-specific polymerase chain reaction. We also performed in vitro analysis to investigate the role of DNMT3A methylation in PTC cell lines. ResultsDNMT3A pathogenic mutations were noted in 1.2% (12/1013) of PTC cases. Reduced/loss of DNMT3A expression was seen in 59.8% (579/968) of PTC cases and was significantly associated with the DNMT3A mutation (p = 0.0120). DNMT3A alterations (mutation and/or loss of expression) were associated with aggressive clinical parameters and a poor outcome. The promoter region of the DNMT3A gene was methylated in 57.1% of PTC cases tested and was significantly associated with reduced DNMT3A protein expression (p = 0.0253). Treatment of the methylated PTC cell line with 5-aza-2′-deoxycytidine resulted in demethylation of the DNMT3A gene, leading to restoration of its expression. Demethylation significantly potentiated the TRAIL-mediated apoptosis in PTC cells. Interestingly, silencing of DNMT3A using siRNA suppressed TRAIL-mediated apoptosis. ConclusionThese findings suggest that DNMT3A alterations play an important role in PTC pathogenesis and demethylation agents can be used to restore the function of DNMT3A in a subset of patients with PTC.

Application of Galectin-3, HBME-1, Cytokeratin-19, and CD56 in the Diagnosis of Thyroid Neoplasm

Objective: The purpose of this study was to investigate the effectiveness of immunohistochemical thyroid malignancy markers Galectin-3, HBME-1, Cytokeratin-19, and CD56 in the diagnosis of thyroid neoplasm. Methods: The study included a total of 53 cases of thyroid neoplasm on which immunohistochemical IHC staining was performed using the manual staining method. Results: The histopathological diagnosis of thyroid nodules was papillary thyroid carcinoma in 40 (75.5%), follicular thyroid carcinoma in 3 (5.7%), follicular adenoma in 8 (15.1%), medullary thyroid carcinoma in 1 (1.9%), and Hurthle cell carcinoma in 1 (1.9%). Out of 40 cases of papillary thyroid carcinoma, Galectin-3 and CK19 were positive in 36 (90%) cases while expression of HBME1 was seen in 32 (80%) papillary thyroid carcinoma cases, and 16 (40%) stained positive for CD56. For the three follicular thyroid carcinoma cases, CD56 was positive in one case, but the marker was positive in 7 out of 8 cases (87.5%) of follicular adenoma. Conclusion: Our results suggest Galectin-3 and HBME-1 are the most sensitive diagnostic markers for differentiating papillary carcinoma from follicular neoplasm.

Clinical and morphological characteristics of papillary thyroid carcinoma associated withhashimoto's thyroiditis

The aim of the work is to study the clinical and morphological features of papillary thyroid carcinoma (PTC) with the autoimmune thyroiditis Hashimoto (TH)Material and methods. 236 clinical observations of patients with PTC of the surgical hospital of he State Institution of Science "Research and Practical Centre of Preventive and Clinical Medicine" State Administrative Department during 2012-2018 were investigated. We study the size of the tumor, the presence of invasions in the thyroid tissue and in the capsule of the gland, multifocal growth, metastases in the lymph nodes of group 6 and metastases in the lymph nodes of 2,3,4 groups. For statistical analysis, Fischer' sex act test and Student's t-criterion were used. Valuesare interpreted by the trueat p &lt;0,05.Results.Of the 236 cases of PTC, TH was found in 72 patients (30.5%), in 56 cases- other proliferative-hyperplastic processesor nodal thyroid pathology (23.7%), and 108 cases (45.8%) were without concomitant pathology. There were 142 (60.2%)women with PTC, and 94 (39.8%) men, p &lt;0.05. In patients with PTC and TH were 53 women (73.6%) and 19 men (26.3%), p &lt;0.05. In patients with TH in comparison with the group without concomitant thyropathology, a significantly higher number of microcarcinoma was noted, the size of tumors in TH was lower (with TH 23 (31.9%), without TH 57 (52.8%), p &lt;0.05 ). In patients without TH, carcinoma invasion was more likely to occur in the thyroid tissue (with TH 32 (44.4%), without TH 66 (61.1%), p &lt;0.05), invasion to the capsule of the gland with extra thyroid invasion (with TH 17 (23.6%), without TX 42 (38.9%), p &lt;0.05), multifocal growth (with TH 15 (20.8%), without TH 48 (44.4%), p &lt;0 , 05). Patients with TH more often had metastasis to the lymphnodes of group 6 (with TH36 (50.0%), without TH 43 (39.8%), p &lt;0.05), and in patients without TH, more often in lateral cervical lymphnodes (with TC 7 (9.7%), without TH 31 (28.7%), p &lt;0.05).Conclusions. 1) PTC with TH more often occur in women. 2) PTC with TH has a less aggressive course regarding the size of the tumor node, intratireoid and extrathyroid invasion, multifocal growth, and metastasis in lateral cervical lymphnodes.

EGFR and CXCR1 expression in thyroid carcinoma in Qassim Region-Saudi Arabia: Correlation with clinicopathological parameters

AimsRecent evidence indicates an increased incidence of thyroid carcinoma, especially papillary thyroid carcinoma (PTC), in Saudi Arabia. EGFR and CXCR1 were reported to have increased expression in several human neoplasms. The goals of the present research was to investigate EGFR and CXCR1 expression in thyroid carcinoma and correlate the results to the established prognostic factors. MethodsImmunohistochemical study for both EGFR and CXCR1 was performed on formalin-fixed paraffin-embedded thyroid carcinomas tissues sections applying Labeled Streptavidin-biotin method (LSAB). ResultsRemarkable high expression of EGFR and CXCR1 were observed in PTC cases (56% and 63% respectively). There was association between EGFR expression in PTC and each of histologic subtype, lymph node metastasis (LNM), distant metastasis (DM), TNM staging and tumor relapse. There was statistical significant correlation between CXCR1 expression in PTC and each of histologic subtype, LNM, and tumor relapse. A significant correlation was detected between concomitant EGFR and CXCR expression and LNM, DM, increasing stage and tumor relapse. ConclusionsThe results of the present study demonstrated, a statistically positive correlation of EGFR and CXCR1 expression in PTC compared to normal thyroid tissues and nodular hyperplasia in Qassim Region- Saudi Arabia. Concomitant high expression of both receptors were strongly correlated with LNM, DM, TNM stage and tumor relapse than did each alone. These findings suggest that EGFR and CXCR1 play crucial roles in PTC and serve as predictors of poor prognosis, biomarkers of tumor diagnosis, and potential targets of cancer therapeutics.

SUN-613 Papillary Thyroid Carcinoma in a Pediatric Patient with Beta Thalassemia

Background: Beta thalassemia is characterized by the abnormal synthesis of β hemoglobin chains resulting in hemolytic anemia. Treatment involves frequent blood transfusions, which leads to the deposition of iron in many organs, including endocrine tissue such as the thyroid gland. Iron overload has been associated with various malignancies, most notably liver and hematological. To date, 7 cases of papillary thyroid cancer in patients with beta thalassemia have been reported in the adult literature, but none in pediatrics. Clinical Case: The patient is a 15 year 4 month old female with beta thalassemia requiring chronic red blood cell transfusions since the age of 5 months. She initially presented to us for evaluation of secondary amenorrhea. She underwent a splenectomy at the age of 10 years and received chelating therapy with deferasirox and deferiprone. Her ferritin levels had been stable around 1500ng/mL for the year prior to presentation; however, MRI revealed iron deposition in her pancreas, liver, kidneys, bone marrow and pituitary gland. On exam, her thyroid gland was asymmetric with the right lobe measuring 1cm larger than the left. The gland was firm in consistency with palpable lymph nodes along the right anterior cervical chain. A thyroid ultrasound was completed which revealed an enlarged right lobe containing 3 focal hypoechoic masses with calcific foci. Biopsy obtained via fine needle aspiration was consistent with papillary thyroid carcinoma. She underwent total thyroidectomy and histological examination confirmed the diagnosis. Her postoperative course was uncomplicated and she was started on replacement therapy with levothyroxine. Conclusion: To our knowledge this is the first case of papillary thyroid carcinoma in a pediatric patient with beta thalassemia. The incidence of thyroid cancer in patients with beta thalassemia is currently unknown, however there may be utility in routine surveillance of this patient population.

SUN-606 Thyroid Cancer Presenting As Acute Limb Ischemia

INTRODUCTION: Cardiac metastases are present in up to 20% of patients with extra-cardiac malignancies and are 40 times more common than primary cardiac tumors. However, thyroid cancer metastatic to the heart is rare. We report a case of mixed follicular and papillary thyroid carcinoma with the presence of anaplastic features presenting with cardiac metastasis. CASE: A 52-year old female non-smoker was admitted with right arm ischemia. Two years earlier, she had been diagnosed with thyroid cancer and underwent total thyroidectomy. Surgical pathology at the time revealed multifocal follicular and papillary thyroid cancer with focal anaplastic changes and positive central lymph nodes. She was treated with 150mCi RAI for remnant ablation, with the post treatment whole-body scan revealing radiotracer activity in the neck but no scintigraphic evidence of distant metastases. She was subsequently lost to follow-up. At the time of admission, she was found to have acute limb ischemia due to axillary artery thrombosis and underwent fasciotomy and embolectomy. Chest CT revealed multiple cavitary lung lesions and a left ventricular mass with adherent thrombus. Biopsy of the lung lesions confirmed metastatic poorly differentiated thyroid cancer (immunohistochemical staining positive for Pax8, TTF-1 and P40, but negative for thyroglobulin). PET scan showed multiple hypermetabolic lesions, including bilateral pulmonary nodules, right hilar adenopathy, a left ventricular mass, and right hepatic lobe lesion. Mutational analysis showed BRAF V600E mutation. The patient is receiving salvage chemotherapy with dabrafenib/ trametinib. DISCUSSION: While rare, follicular carcinoma is the most common thyroid cancer with cardiac metastasis, mostly involving the central veins and right atrium. Papillary thyroid cancer tends to metastasize through the lymphatic system and involve the right side of the heart. The aggressive behavior of our patient’s tumor, with involvement of the left heart suggestive of vascular metastasis, is likely due to the concurrent presence of anaplastic de-differentiation. Anaplastic carcinomas are highly aggressive neoplasms and 71% are said to occur simultaneously with a well-differentiated thyroid cancer. About 50% of patients diagnosed with anaplastic thyroid cancer have metastatic disease at the time of diagnosis and another 25% develop metastasis during the course of disease. The prognosis is very poor with median survival ranging from 4-12 months.

The co-relation of BRAF V600E mutation and factors affecting occurrence and prognosis of papillary thyroid carcinoma

Objective: To investigate the prevalence of BRAF V600E mutation in thyroid nodules and to analyze the relationship between BRAF V600E mutation and various clinicopathological features. Methods: BRAF V600E mutant gene test was done in 463 cases of thyroid nodules collected from April 2015 to July 2018 in Beijing Hospital. Pathologic sections of 444 cases of papillary thyroid carcinoma were reviewed and clinical information was collected.Statistical analysis of the relationship between BRAF V600E gene mutation and various clinicopathological features was performed with SPSS 21.0 statistical software. Results: There were 109 males and 354 females in the cohort, with a male to female ratio of 1.0∶3.2. The patient ranged in age from 16 to 82 years, with an average age of 46.1 years. The BRAF V600E mutation rates in papillary thyroid carcinoma, benign thyroid nodules and other thyroid carcinoma were 86.5%(384/444),0/15 and 1/4,respectively.There was significant correlation between BRAF V600E mutation and histological diagnosis of papillary thyroid carcinoma (P<0.05). There was no correlation with age, gender, multifocality, bilaterality, coexisting lymphocytic thyroiditis, nodular goiter, maximum diameter, capsule invasion, extrathyroidal extension and clinical stage (P>0.05). Conclusions: BRAF V600E gene mutation is closely related to the occurrence of papillary thyroid carcinoma. BRAF V600E has significant value in the diagnosis of papillary thyroid carcinoma. While BRAF V600E mutation is related to the histological diagnosis, it shows no correlation with other clinicopathologic features. BRAF V600E mutation is not an independent prognostic factor in papillary thyroid carcinoma patients.

Clinical and pathologic analysis of 2684 cases of papillary thyroid carcinoma in 8 years

Objective:To study the clinicopathological and annual features of PTC patients in the past 8 years. Method: Review the clinicopathological data of PTC patients treated by surgery for the first time in the First Affiliated Hospital of Xi'an Jiaotong University from 2010 to 2017. Result: The total number of PTC patients was 2684, which was increasing from 2010 to 2017. The peak age of onset of PTC was 31-60 years old, and the highest peak age was 41-55 years old, including 41-45 years for men and 46-50 years for women. There was no significant difference in the average age of PTC patients during the 8 years(P>0.05). The total male/female ratio oscillated between 1.00：2.91 and there was no significant difference(P>0.05). The increase in the number of male and female patients was approximately parallel. Both had an upward trend(P<0.05). The proportions of multifocal and singletumor cancers were nearly parallel in the 8 years, and there was no significant difference(P>0.05). The percentage of PTC combined with HT increased year by year(P<0.05). The percentage of PTMC showed an increasing trend year by year(P<0.05). The rate of lymph node metastasis in the central area of PTMC was 15.81%. Conclusion: During the past 8 years, the growing number of PTC patients with different genders was approximately parallel. There was no significant difference in the average age and total male/female ratio of PTC patients. The proportions of multifocal and single-tumor cancers were nearly parallel. The percentage of PTC combined with HT has been increasing year by year. The percentage of PTMC showed an increasing trend. .

MiR-506 suppresses papillary thyroid carcinoma cell proliferation and metastasis via targeting IL17RD.

The aim of this study was to determine the role of microRNA-506-3p (miR-506) in papillary thyroid carcinoma (PTC), and to further explore the underlying mechanism. The expression level of miR-506 in clinical cases was detected by Real Time-fluorescence quantitative Polymerase Chain Reaction (RT-qPCR). Meanwhile, RT-qPCR was performed to determine miR-506 expression in different PTC cell lines. Bioinformatics software was used to predict the possible target genes of miR-506. Dual-Luciferase reporter gene assay together with Western blot (WB) assay were used to verify the prediction results. Finally, cellular functions such as proliferation and metastasis capacities were detected in vitro. RT-qPCR was used to measure the expression level of miR-506 in 80 paired PTC cases. The results showed that the expression level of miR-506 in PTC tissues was significantly decreased. In vitro, miR-506 expression was also markedly suppressed in four PTC cell lines. TPC-1 cells expressed the lowest level of miR-506. Subsequently, the target gene of miR-506 was predicted by TargetScan, miRBase and miRanda. The prediction results indicated that IL17RD was an alternative target gene of miR-506. Furthermore, miR-506 was found to remarkably inhibit the Luciferase activity of wild-type IL17RD. However, it had no effect on mutant-type. Besides, the protein expression level of IL17RD was significantly reduced in miR-506-overexpressing TPC-1 cells. More importantly, the restored expression of IL17RD could alleviate the blocking effects of miR-506 on cell proliferation, migration and invasion. In this study, we found that miR-506 could inhibit the proliferation and metastasis of PTC cells. Meanwhile, IL17RD might be a downstream target of the biological process. Our findings provided a new therapeutic direction for the treatment of PTC.

Association between BRAF (V600E) mutation and clinicopathological features of papillary thyroid carcinoma: a Brazilian single-centre case series.

We aimed to investigate the prevalence of the BRAF (V600E) mutation in consecutive cases of papillary thyroid carcinoma (PTC) in patients diagnosed and treated at the Hospital Sao Rafael (Salvador, BA, Brazil) and evaluate its association with clinical and pathological characteristics of PTC. We retrospectively enrolled in the study a total of 43 consecutive PTC patients who underwent total thyroidectomy. We performed DNA extraction from formalin-fixed paraffin-embedded (FFPE) tumour tissue samples. Polymerase chain reaction (PCR) and direct sequencing were used to determine BRAF (V600E) mutation status. Univariate and multivariate logistic regression analyses were employed to identify independent associations. The prevalence of BRAF (V600E) mutation was 65.1% (28/43). A high frequency of older patients (p value: 0.004) was observed among the BRAF-mutated PTC group and, in contrast, a low frequency of concurrent Hashimoto's thyroiditis (HT) (p value: 0.011) was noted. Multivariate analysis confirmed that older age (OR: 1.15; 95% CI: 1.00 - 1.33; p value: 0.047) and HT (OR: 0.05; 95% CI: 0.006-0.40; p value: 0.005) were independent factors associated with BRAF (V600E) mutation. We found a high prevalence of BRAF (V600E) mutation in PTC cases. Older age and no concurrent HT were independently associated with BRAF (V600E) mutation.

Investigation of the clonal origin of multifocal papillary thyroid carcinoma according to the X-chromosome inactivation pattern.

Patients with papillary thyroid carcinoma (PTC) usually have multiple tumors, or foci. It remains unclear if these foci originate from independent tumors or a single tumor mass. The present study included 89 female patients with bilateral PTC who had been treated with a total thyroidectomy. An X-chromosome inactivation assay was used to examine the clonal origin of the tumors according to the status of the X-linked human androgen receptor gene. Of the 89 patients, 5 were informative. The X-chromosome inactivation pattern was the same in multiple foci in 3 cases, indicating a monoclonal origin of the tumors. In 1 case, the X chromosome inactivation pattern was different between the tumors. Mixed patterns were observed in 1 case. The results of the present study suggest that in certain cases of multifocal PTC, tumors arise independently, whereas in other cases, separate foci are the outcome of intra-thyroid spread by a single tumor mass.

Relationship between genetic alterations and clinicopathological characteristics of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is characterized by proliferation of follicular cells with distinctive nuclear features such as ground glass appearance, nuclear groove and pseudoinclusion. From the proliferation pattern, PTC is divided into several histological subtypes; conventional histology is classified as papillary type, and there are also follicular and solid variants. PTC is heterogeneous in genetic alterations. PTC with BRAF mutation presents a histology of conventional PTC, and follows an aggressive clinical course. Most cases of PTC with RAS mutation show a follicular variant, and prognosis is favorable. RET/PTC1 is observed sporadically and in young cases, and prognosis is favorable. RET/PTC3 is associated with radiation exposure, and the solid variant is frequent. ETV6-NTRK3 may be associated with radiation exposure, and the clinical course is aggressive. Mutation in the telomerase reverse transcriptase promoter is observed in PTC cases involving elderly male patients. Tumor size is large, associated with distant metastasis and advanced stage. This mutation is found concomitantly with BRAF mutation, and the clinical course is aggressive. Genetic alterations form subsets of PTC with distinct clinicopathological features. Careful assessment of clinicopathological features is considered useful in predicting clinical course and when planning treatment.

Loss of Heterozygosity (LOH) at 17p13 and 22q13 are Shared by Breast and Thyroid Carcinomas for Metastasis.

Many genomic mutations have been identified to be related to the metastasis of malignancies from various primary sites. In this study, we attempted to identify the loss of heterozygosity (LOH) that might be involved in metastasis of breast ductal carcinoma (BDC) and papillary thyroid carcinoma (PTC). We retrieved 14 BDC cases with metastasis and 19 BDC cases without metastasis as well as 12 PTC cases with metastasis and 14 PTC cases without metastasis. Analysis of 13 polymorphic microsatellite repeat markers targeting 1p34-36, 3p24-26, 9p21, 10q23, 17p13, 17q21, 21q22, and 22q13 was performed on DNA isolated from primary tumors. The results showed that LOH at 17p13 and 22q13 was shared by both BDC and PTC for metastasis. More detailed studies to identified genes in these shared loci of LOH may provide further insight into the molecular mechanisms underlying metastases in these 2 tumor types, and possibly other malignancies as well.