papillary thyroid cancer

This research examined the connection between circulating FGF21 and clinicopathological findings in papillary thyroid carcinoma.

This analytical cross-sectional research was conducted on patients with papillary thyroid cancer at the Seyyed Shirazi Endocrinology Clinic in Gorgan, Iran. Laboratory data, including demographics, ultrasonography and pathology reports, and FGF21 levels, were collected. The data was analyzed with SPSS 25. Normal distribution was evaluated by using Kolmogorov-Smirnov and Shapiro-Wilk tests. Group differences were evaluated with Chi-square, independent sample t-test and Mann-Whitney U tests. A p-value less than 0.05 was considered significant.

In this research, 83% of patients were female, and the mean±SD age was 42.51±13.28 years old. The mean±SD and FGF21 concentrations in 49 patients were 716.41±458.7, the median was 489 pg/ml, and 24 (49%) patients were in the high FGF21 group. There was no statistically significant relation between FGF21 level and age (P=0.95), sex (P=>0.99), tumor size (P=0.68), tumor stage (P=>0.99), lymphadenopathy (P=>0.99), lymph node metastasis (P=0.24), triglycerides (P=0.93), total cholesterol (P=0.47), LDL (P=0.08), and HDL (P=0.08). However, FGF21 levels were significantly associated with fasting blood glucose (P=0.03), body mass index (BMI) (P=<0.0001), capsular invasion (P=0.001), lymphovascular involvement (P=0.0001) and Thyroid Imaging Reporting and Data System (TIRADS) score (P=0.02). In addition, high levels of FGF21 were found to be 78.95% sensitive and 70% specific for capsular invasion.

Our study demonstrated that FGF21 is associated with more severe papillary thyroid cancer clinicopathological features such as capsular invasion, lymphovascular involvement, TIRADS score, and BMI.

Papillary thyroid carcinoma is the most frequent type of thyroid cancer. The BRAFV600E mutation is associated with tumor progression. We explored the utility of the BRAF molecular testing on fine needle aspiration fixed specimens of patients with confirmed diagnoses of papillary thyroid carcinoma.  

Fixed thyroid cytology slide specimens of 19 patients with Bethesda II to VI reports were used to detect BRAFV600E mutation by pyrosequencing of extracted DNA.   

BRAFV600E mutation was detected in 25% of the specimens with Bethesda category III and IV nodules and in 73% of the nodules with Bethesda category V and VI.   

BRAF mutation analysis can be performed on fixed fine needle aspiration cytology specimens. Although the frequency of the mutation is higher in specimens with higher Bethesda category scores, it could support clinical decision-making in thyroid nodules with intermediate Bethesda category scores.

 Thyroid cancer is the most common endocrine cancer, and women are almost three times more likely to develop it than men.

 The etiology of thyroid cancer at the genetic level remains elusive. However, a potential involvement of the RNA Transcription, Translation, and Transport Factor (RTRAF) gene in the pathogenesis of this malignancy has been postulated. This gene has been shown to govern the expression of proteins that exert regulatory effects on the transition from the G1 to S phase of the cell cycle.

 For this study, 22 papillary thyroid carcinoma (PTC) tissues and 22 healthy tissues were collected. Additionally, 10 benign goiter tissues and 10 healthy tissues were gathered. RNA molecules were fixed, and complementary DNA (cDNA) was produced. Specific primers were used to measure the RTRAF gene expression. Statistical analysis was conducted using REST 2009 software.

 Upon assessing the quality and quantity of RNA, it was ascertained that the extracted RNA molecules exhibited minimal damage and were found to be appropriately concentrated for cDNA production. The amplification of the RTRAF gene was carried out accurately, as evidenced by the melting curve. A noteworthy decline in the RTRAF gene expression was detected in the benign goiter tissue compared to the adjacent healthy tissue, with a relative expression of 0.154 and a statistical value of P = 0.002. Conversely, there was no significant difference in the RTRAF gene expression between PTC and the adjacent healthy tissue, with a P-value of 0.808.

 The reduced RTRAF gene expression in benign thyroid tumors may hinder cancer cell growth, as no difference was observed between malignant PTC tumor tissues and their healthy tissues.

Detection of cancer in patients with thyroid nodules requires sensitive and specific diagnostic modalities that are accurate and inexpensive. This study aimed to identify a potential microRNA(miRNA) panel to detect papillary thyroid carcinoma (PTC).

Following a comprehensive literature review as well as miRNA target predictor databases, Real-time PCR was used to quantify the expression of candidate miRNAs in 59 tissue specimens from 30 patients with PTC and 29 patients with benign nodules. A receiver operating characteristic (ROC) curve analysis was used to assess the accuracy of miRNA expression levels compared to the pathology report as the gold standard. Based on prediction results, four miRNAs, including miR-9, miR-20b, miR-221, and miR-222, were selected to evaluate their expression level in Iranian thyroid samples.

A significant difference between the tissue expression level of miR-20b, miR-9, miR-222, and miR-221 was detected in the PTC group compared with non-PTC (P < 0.05). The area under the curves for the included miRs were 1, 0.98, 0.99, 0.98, and 1, respectively.

Our results confirmed deregulations of miR-20b as well as miR-222, miR-221, and miR-9 in PTC and, therefore, could be used as a helpful miRNA panel to differentiate PTC from benign nodules, which results in the more efficient clinical management of PTC patients.

 There are inconsistent results of studies on accuracy of 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (2-[18F]FDG-PET/CT) for cervical lymph node (LN) staging. The aim of this study is to evaluate the accuracy of 2-[18F]FDG-PET/CT in the cervical LN staging of patients with papillary thyroid cancer (PTC) and the factors associated with false-positive LNs in these patients.

 A total of 234 patients with pathologically proven PTC, who underwent 2-[18F]FDG-PET/CT for staging from January 2011 to December 2014, were analyzed. The gold standard for diagnosing LN is a combination of surgical pathology and clinical follow-up. Nodal uptake with a maximum standardized uptake value (SUVmax) > 2.0 was interpreted as PET/CT-positive.

 The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 2-[18F]FDG-PET/CT in detecting cervical LN metastases were 42.7% (41/96), 77.7% (248/319), 36.6% (41/112), 81.9% (248/303), and 69.6% (289/415), respectively. The incidence of false-positive LN metastases was 63.4% (71 of 112 LNs). The factors significantly associated with false positives were age < 45 years old (p = 0.032) and SUVmax of the primary tumor < 4.0 (p = 0.021). In addition, false-positive LNs were correlated with a low LN SUVmax, location (central vs. lateral), and direction (ipsilateral vs. contralateral).

 These findings suggest that cervical LN staging by 2-[18F]FDG-PET/CT in PTC patients should be more carefully assessed in patients younger than 45 years old with a primary tumor SUVmax < 4.0 or contralateral LN.

Papillary thyroid cancer (PTC) is the most common primary cancer originating from thyroid follicular cells. The aim of this study was to evaluate the positive predictors of micrometastasis in central lymph nodes in patients with papillary thyroid cancer.

This was a cross-sectional study. The study population was all known PTC patients who underwent total thyroidectomy and lymph node dissection of the central neck nodes based on the current indications. Confirmation of central lymph node involvement was performed by permanent smear after surgery. Data were analyzed using SPSS software version 22. A P-value below 0.05 was considered statistically significant.

There was no significant relationship between age, gender, family history of PTC, family history of thyroid disease, multinodularity, history of other thyroid diseases, involvement of two thyroid lobes, and tumor grade with central lymph node involvement (P>0.05). There was a significant relationship between the tumor pathology and size with central lymph node involvement (P<0.05). Moreover, logistic multivariate regression analysis showed that female gender, multinodularity, and tumor size had a significant relationship with the incidence of central lymph node involvement (P<0.05).  

Female gender, multinodularity, and larger tumor size may be predictors of micrometastasis in central lymph nodes in patients with papillary thyroid cancer.

The initial post-surgical radioactive iodine (RAI) therapy for patients with papillary thyroid cancer (PTC) is postponed due to increased demand as well as the limited number of centers to provide RAI therapy. Hence, our aim was to investigate the role of first RAI administration time following thyroidectomy on the number of incomplete response (IR) during the initial follow up, while considering other prognostic factors. Two hundred and thirty-five PTC patients who were admitted to our department for RAI therapy were included in this study. They were allocated into two groups with <3 months (early group) and ≥ 3 months (delayed group) time interval after the first RAI therapy, and the total thyroidectomy. Then, based on the response to RAI therapy, patients were categorized as excellent, biochemical incomplete, structural incomplete, or indeterminate responses (ER, BIR, SIR or IDR, respectively). With respect to age, gender, pathologic variables, RAI dose rate and IR (BIR+SIR) rate, significant differences were found between the two groups. The findings identified that early RAI failed to affect the rate of IR (univariate analysis: HR=1.09, 95%CI: 0.69-1.74, P=0.71; Cox model: HR=0.81, 95%CI: 0.46-1.44, P=0.47). However, Cox multivariate analysis found lymph node status and thyroglobulin level (Lymph node status: HR=2.88, 95%CI: 1.07-7.78, P=0 .04) as independent risk factors for IR during the initial follow up. Therefore, timing of the first post-surgery RAI therapy is not a significant prognosticator of the initial response of patients to therapy.

The kidney is an unconventional site for thyroid metastasis. As of the writing of this article, only about 30 cases have been reported. It presents like a renal mass. We are reporting a man with thyroid carcinoma presenting with distant metastasis to the kidney. He had complaints of abdominal pain and haematuria. Initial imaging suggested a left renal mass. A diagnosis of renal cell carcinoma was made and a nephrectomy was performed. Histopathology revealed it to be a metastasis from cancer of the thyroid gland. Subsequently, an ultrasound of the thyroid gland was performed, which showed a malignant appearing thyroid nodule. Correlative bone scan showed uptake at multiple skeletal sites. Total thyroidectomy was done and it was found to be papillary thyroid cancer. Subsequently, high dose radioactive iodine was administered. The patient was followed up and has recently found to have metastasis to the brain and is undergoing radiotherapy.

This study was attempted to investigate the prevalence of BRAF gene mutation (V600E) in aspiration cytology of patients with suspected papillary thyroid carcinoma (PTC).

Seventy six Patients suspected of having PTC who referred for fine needle aspiration (FNA) biopsy were included in this cross-sectional study. Ultrasound-guided FNA was taken from the thyroid masses and samples were sent for cytologic evaluation. Simultaneously, the samples were sent to a genetic laboratory to check the status of BRAFV600E mutation. Patients with FNA positive for PTC were assigned in one group and those with FNA negative for PTC were assigned in other group. Cytological and molecular results were compared with those of histopathology and sonography.

The results showed that the prevalence of the BRAF gene (V600E) mutation in our study was 21.1% (16 out of 76 patients). In addition the results showed a significant relation between gene mutation and pathologic findings so that the highest gene mutation was significantly detected in patients with FNA positive for PTC (p.value=0.001). Also, our results showed a significant relation between gene mutation and some sonographic findings (calcification, p.value=0.004) and no significant relation in the other sonographic findings (hypo echoic changes, p.value=1.12 and regular changes, p.value=0.194).

According to the results of the present study, BRAF mutation (V600E) can be an effective indicator for definitive diagnosis and primary treatment of PTC in suspected cases.

Thyroid cancer is the most prevalent type of endocrine malignancy with the highest incidence rate among women under 45 years old. Ethinylestradiol (EE) and levonorgestrel (LNG) are two steroid components of low-dose oral contraceptives used all over the world. In this study, we aimed to examine the possible effects of the combination of these two steroids on metastasis and angiogenic factors in BCPAP papillary thyroid cancer (PTC) cell line. After treatment of BCPAP cells with the combination of 20 nM EE and 90 nM LNG, mRNA expression levels of long noncoding RNAs HOTAIR and MALAT1, angiogenic and antiangiogenic gene markers VEGFA and THBS1, and epithelial-mesenchymal transition (EMT) biomarkers CDH1, CDH2, FN1, and VIM were analyzed by real-time PCR. Additionally, the protein expression of VEGFA was semiquantified by Western blotting. Results showed that the combination of LNG and EE significantly elevated the level of VEGFA protein and mRNA expression of VEGFA, MALAT1, HOTAIR, CDH2, FN1, and VIM genes while decreased CDH1 gene expression but had no marked effect on the expression of THBS1 gene in comparison with the control group. Also, our results suggest that LNG and EE may increase the metastatic and migratory properties of BCPAP cells via modulating angiogenic and EMT biomarkers. These data may highlight the potential of exogenous steroids in the advancement of PTC tumors.

In patients with papillary thyroid cancer (PTC), sentinel lymph node (SLN) radio-guided biopsy is not routinely used for detection of involved neck lymph nodes (NLN); 99mTc-sulfur colloid antimony (99mTc-SC) has been used for this purpose. In this study, besides 99mTc-SC another radiotracer, 99mTc-phytate (99mTc-P) with different doses and injection methods were evaluated. Twenty-two patients, scheduled to undergo thyroidectomy for PTC, were injected for radio-guided SLN biopsy in the morning of operation in 3 groups: intra tumoral injection of about 1 mCi 99mTc-P (group A; n=5); peritumoral injection of less than 3 mCi 99mTc-SC (group B; n=6); and peritumoral injection of 3 to 5 mCi 99mTc-SC with application of massage (group C; n=9). A patient refused to complete the study. No NLN was detected in the pre-operative ultra-sonographic examinations of all patients. Central neck dissection was done for all the participants. The presence of radio guided detected NLN and results of pathology were assessed. In group A and B, no SLN was detected. NLNs were resected in 4 patients in group A and B; 2 of them involved by the tumor. In group C, 6 out of 9 patients (66.7%) had between 1 to 6 SLNs; the procedure failed to detect SLN in a patient in group C with surgically resected reactive NLN (failure rate 1 out of 7). The results underscored the significance of SLN radio guided biopsy in patients with PTC; the radiotracer, dose and method of injection may affect the detection rate.

Papillary thyroid carcinoma (PTC) is a common subtype of thyroid carcinoma with a rising incidence rate. The purpose of this study was to provide a better understanding of age and PTC using the Surveillance, Epidemiology, and End Results (SEER) Program.

The study derived patients’ information from the SEER Program (2010–2015). Chi-square or Fisher exact tests, and Kaplan–Meier method were used to analyze survival. Prognostic factors associated with survival were analyzed by Cox multivariate regression.

A total of 1738 records were included from SEER, with 1079 PTC in the age group <55 years, and 659 PTC in the age group ≥55 years. The 5-year survival rate was 94% and the overall survival (OS) curve in different age groups indicated that patients younger than 55yr have a longer survival time (P<0.05). In multivariate Cox regression, age, M stage and surgery treatment were independent risk factors (P<0.05). Regarding PTC-specific survival, age and surgery treatment were the two main independent prognostic factors in multivariate regression. However, AJCC and M stage were not in the disease specific survival.

Age is a prognostic factor in OS and PCT specific survival. AJCC I stage and surgery treatment are also significant in predicting prognosis

Metastasis to lymph nodes and distant organs is the main challenge in the treatment of papillary thyroid cancer. In the current investigation, we aimed to evaluate the synergistic effects of celecoxib (CX) and sodium valproate (VPA) against cell survival, invasiveness properties, and expression of metalloproteinase-2 and -9 (MMP-2 and MMP-9) in papillary thyroid cancer cell line, BCPAP cells. The effect of CX and VPA on B-CPAP cells viability and apoptosis were investigated using MTT assay and annexin V/7-AAD flowcytometry, respectively. The effects of the drugs on invasiveness properties of B-CPAP cells and expression of MMP-2 and MMP-9 were evaluated using transwell assay and real time PCR, respectively. MTT assay showed that CX and VPA decreased viability of B-CPAP cells dose dependently (IC50 32.4µM and 6.8 mM, respectively). Combination of CX (5 μm) and VPA (2.5 and 5 mM) increased apoptosis, and reduced cell migration and invasion of B-CPAP cell, synergistically. Real time PCR results showed that both CX (5 µM) and VPA (2.5 and 5 mM) reduced MMP-2 expression (P

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The aim of this study was to investigate the association of tissue inhibitor metalloproteinase-3 (TIMP3) mRNA and protein levels in thyroid tissues, based on BRAF V600E status with the clinicopathologic characteristics of PTC.
A total of 60 fresh frozen tissue samples of PTC patients (15 male and 45 female) were collected during thyroidectomy. All clinicopathological information was obtained and samples were reviewed as well as confirmed by a pathologist; exon 15 of the BRAF gene was genotyped by sequencing, TIMP3 mRNA level was assessed using SYBR-Green Real-Time PCR, and TIMP3 protein level was measured using ELISA.
Of 60 cases, BRAF mutation was found in 24 (40%). Larger tumor size and higher lymph node metastasis frequency were observed, significant in BRAF (), compared to the BRAF (-) PTC group (P = 0.039 and P = 0.03, respectively). No significant difference was seen in the tumoral tissues of the TIMP3 mRNA level in BRAF (), compared to BRAF (-) PTC samples. However, the mean TIMP3 protein level was significantly lower in tumoral tissues, compared to matched non-tumoral tissues in BRAF () PTC (P=0.003); TIMP3 protein level was significantly lower in tumoral tissues compared to matched non-tumoral tissues in BRAF (), in subjects who had no lymph node metastasis and also in subjects with lymph node metastasis in both BRAF positive and negative PTC cases.
Our results showed that BRAF mutation was associated with a larger tumor size, higher frequency of lymph node metastasis, and lower TIMP3 protein levels. Lower TIMP3 protein level was associated with the lymph node metastasis in PTC patients.

Soft tissue metastases are extremely rare in differentiated thyroid cancers. We hereby present a man with a history of papillary thyroid cancer (PTC) at the age of 46, who was referred to cancer Institute due to raised serum thyroglobulin (Tg) and a new mass in the thigh. Imaging studies were suggestive of recurrence of the disease in the tumor bed, neck nodes and lungs, and also a mass in his left thigh, based on positron emission tomography (PET) scan, without radioactive iodine uptake. The excision of the mass revealed metastatic PTC. After management of symptomatic local recurrence with external beam radiotherapy (EBRT), he received sorafenib. After three years he is doing well and serum Tg is stable.