Showing papers on "Papillary thyroid cancer published in 2015"

Association Between BRAF V600E Mutation and Recurrence of Papillary Thyroid Cancer

Abstract: Purpose To investigate the prognostic value of BRAF V600E mutation for the recurrence of papillary thyroid cancer (PTC). Patients and Methods This was a retrospective multicenter study of the relat...

Redifferentiation of iodine-refractory BRAF V600E-mutant metastatic papillary thyroid cancer with dabrafenib.

Abstract: Purpose: To determine whether the selective BRAF inhibitor, dabrafenib, can stimulate radioiodine uptake in BRAF V600E-mutated unresectable or metastatic iodine-refractory papillary thyroid cancer (PTC). Experimental Design: Ten patients with BRAF V600E-mutant iodine-refractory PTC were enrolled. Absence of radioiodine uptake on iodine-131 whole body scan obtained within 14 months of study entry was required. Each patient received dabrafenib (150 mg twice daily) for 25 days before thyrotropin α-stimulated iodine-131 whole body scan (4 mCi/148 MBq). Patients whose scan showed new sites of radioiodine uptake remained on dabrafenib for 17 more days, and then were treated with 150 mCi (5.5 GBq) iodine-131. The primary endpoint of the study was the percentage of patients with new radioiodine uptake after treatment with dabrafenib. Results: Six of 10 patients (60%) demonstrated new radioiodine uptake on whole body scan after treatment with dabrafenib. All 6 were treated with 5.5 GBq iodine-131. Two patients had partial responses and 4 patients had stable disease on standard radiographic restaging at 3 months. Thyroglobulin decreased in 4 of 6 treated patients. One patient developed squamous cell carcinoma of the skin. There were no other significant adverse events attributed to dabrafenib. Conclusions: Dabrafenib can stimulate radioiodine uptake in patients with metastatic BRAF V600E-mutant iodine-refractory PTC, representing a potential new therapeutic approach for these patients. Clin Cancer Res; 21(5); 1028–35. ©2014 AACR .

Presence and Number of Lymph Node Metastases Are Associated With Compromised Survival for Patients Younger Than Age 45 Years With Papillary Thyroid Cancer

Abstract: Purpose Cervical lymph node metastases are recognized as a prognostic indicator only in patients age 45 years or older with papillary thyroid cancer (PTC); patients younger than age 45 years are perceived to have low-risk disease. The current American Joint Committee on Cancer staging for PTC in patients younger than age 45 years does not include cervical lymph node metastases. Our objective was to test the hypothesis that the presence and number of cervical lymph node metastases have an adverse impact on overall survival (OS) in patients younger than age 45 years with PTC. Patients and Methods Adult patients younger than age 45 years undergoing surgery for stage I PTC (no distant metastases) were identified from the National Cancer Data Base (NCDB; 1998-2006) and from SEER 1988-2006 data. Multivariable models were used to examine the association of OS with the presence of lymph node metastases and number of metastatic nodes. Results In all, 47,902 patients in NCDB (11,740 with and 36,162 without nodal me...

Prophylactic Central Compartment Lymph Node Dissection in Papillary Thyroid Carcinoma: Clinical Implications Derived From the First Prospective Randomized Controlled Single Institution Study

Abstract: Background: The benefits of prophylactic central compartment lymph node dissection (pCCND) in papillary thyroid cancer (PTC) are still under investigation. This treatment seems to reduce PTC recurrence/mortality rates but has a higher risk of surgical complications. The lack of prospective randomized trials does not allow definitive recommendations. The aim of this prospective randomized controlled study was to evaluate the clinical advantages and disadvantages of pCCND. Patients: A total of 181 patients with PTC without evidence of preoperative/intraoperative lymph node metastases (cN0) were randomly assigned to either Group A (n = 88) and treated with total thyroidectomy (TTx) or Group B (n = 93) and treated with TTx + pCCND. Results: After 5 years of followup, no difference was observed in the outcome of the two groups. However, a higher percentage of Group A were treated with a higher number of 131I courses (P = .002), whereas a higher prevalence of permanent hypoparathyroidism was observed in Group B...

Adjuvant Radioactive Iodine Therapy Is Associated With Improved Survival for Patients With Intermediate-Risk Papillary Thyroid Cancer

Abstract: Context: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The long-term prognosis is generally excellent. Due to a paucity of data, debate exists regarding the benefit of adjuvant radioactive iodine therapy (RAI) for intermediate-risk patients. Objective: The objective of the study was to examine the impact of RAI on overall survival in intermediate-risk PTC patients. Design/Setting: Adult patients with intermediate-risk PTC who underwent total thyroidectomy with/without RAI in the National Cancer Database, 1998–2006, participated in the study. Patients: Intermediate-risk patients, as defined by American Thyroid Association risk and American Joint Commission on Cancer disease stage T3, N0, M0 or Mx, and T1–3, N1, M0, or Mx were included in the study. Patients with aggressive variants and multiple primaries were excluded. Main Outcome Measures: Overall survival (OS) for patients treated with and without RAI using univariate and multivariate regression analyses was measured. Results: ...

Low-Risk Differentiated Thyroid Cancer and Radioiodine Remnant Ablation: A Systematic Review of the Literature

Abstract: Background: Radioiodine remnant ablation (RRA) has traditionally been one of the cornerstones of differentiated thyroid cancer (DTC) treatment. The decision to use RRA in low-risk (LR) and intermediate-risk (IR) patients is controversial. The aim of this review is to examine the evidence of RRA benefit in the staging, follow-up, and recurrence prevention in LR and IR DTC patients. Methods: From a PubMed search, we selected original papers (OPs) using the following inclusion criteria: 1) DTC; 2) LR and IR patients; 3) non-RRA-treated patients or RRA-treated vs non-RRA-treated groups; 4) a report of the outcome of cancer recurrence; and 5) publication since 2008. Results: Neck ultrasonography is superior to whole-body scan for disease detection in the neck. A rising or declining serum thyroglobulin level over time provides an excellent positive or negative predictive value, respectively, even in non-RRA-treated patients. No OP demonstrating RRA benefit on recurrence in LR patients was found; two OPs found n...

Recurrence of papillary thyroid cancer after optimized surgery

Abstract: Recurrence of papillary thyroid cancer (PTC) after optimized surgery requires a full understanding of the disease, especially as it has changed in the last 15 years, what comprises optimized surgery, and the different types and implications of disease relapse that can be encountered. PTC has evolved to tumors that are much smaller than previously seen, largely due to various high quality imaging studies obtained for different reasons, but serendipitously identifying thyroid nodules that prove to be papillary thyroid microcarcinomas (PTMC). With rare exception, these cancers are cured by conservative surgery without additional therapy, and seldom result in recurrent disease. PTC is highly curable in 85% of cases because of its rather innocent biologic behavior. Therefore, the shift in emphasis from disease survival to recurrence is appropriate. As a result of three technologic advances—high-resolution ultrasound (US), recombinant TSH, and highly sensitive thyroglobulin (Tg)—disease relapse can be discovered when it is subclinical. Endocrinologists who largely control administration of radioactive iodine have used it to ablate barely detectable or even biochemically apparent disease, hoping to reduce recurrence and perhaps improve survival. Surgeons, in response to this new intense postoperative surveillance that has uncovered very small volume disease, have responded by utilizing US preoperatively to image this disease, and incorporated varying degrees of lymphadenectomy into their initial treatment algorithm. Bilateral thyroid resection— either total or near-total thyroidectomy—remains the standard for PTC >1 cm, although recent data has reemphasized the value of unilateral lobectomy in treating even some PTC measuring 1-4 cm. Therapeutic lymphadenectomy has universal approval, but when lymph nodes in the central neck are not worrisome to the surgeon’s intraoperative assessment, although that judgment in incorrect up to 50%, whether they should be excised has reached a central point of controversy. Disease relapse can occur individually or in combination of three different forms: lymph node metastasis (LNM), true soft tissue local recurrence, and distant disease. The latter two are worrisome for potentially life-threatening consequences whereas nodal metastases are often persistent from the initial operation, and mostly comprise a biologic nuisance rather than virulent disease. A moderate surgical approach of bilateral thyroid resection, with usual central neck nodal clearance, and lateral internal jugular lymphadenectomy for node-positive disease can be performed safely, and with about a 5% recurrence rate.

Papillary thyroid cancer: dual-energy spectral CT quantitative parameters for preoperative diagnosis of metastasis to the cervical lymph nodes.

Abstract: Compared with qualitative assessment of conventional CT imaging features, quantitative assessment of gemstone spectral imaging parameters, especially the combination of venous phase slope of the spectral Hounsfield unit curve and arterial phase normalized iodine concentration, showed higher accuracy for the preoperative diagnosis of metastasis to the cervical lymph nodes in patients with papillary thyroid cancer.

Efficacy and Tolerability of Vemurafenib in Patients with BRAFV600E -Positive Papillary Thyroid Cancer: M.D. Anderson Cancer Center Off Label Experience

Abstract: Context: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAFV600E mutation. Objective: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial. Design: A retrospective review at MD Anderson Cancer Center. Methods: The best responses were evaluated using RECIST v1.1. A single radiologist reviewed all images. Adverse events (AEs) were evaluated using CTCAE v.4.0. Results: We identified 17 patients with advanced PTC harboring the BRAFV600E mutation who were treated with vemurafenib outside of a clinical trial. Median age at diagnosis was 63 years, and 53% were male. At vemurafenib start, 3 (18%) patients had disease confined to the neck, and 14 (72%) had distant metastases. Tyrosine kinase inhibitors had been previously administered to 4 (24%) patients. Two (12%) patients discontinued vemurafenib because of AEs before restaging. Best response: partial response (PR) in 7/15 (47...

Efficacy and safety of radiofrequency ablation for treating locoregional recurrence from papillary thyroid cancer.

Abstract: To assess the efficacy and safety of ultrasound- (US) guided radiofrequency ablation (RFA) for controlling locoregional recurrent papillary thyroid cancer (PTC) in a large patient population. We included patients who had undergone RFA for locoregional recurrent PTC between September 2008 and April 2012 who fulfilled the following criteria: no metastasis beyond the neck; not more than four tumours; confirmed recurrence by US-guided fine needle aspiration biopsy or thyroglobulin measurement of needle washouts; more than a six-month follow-up period; and surgery not feasible or was refused by the patient. Sixty-one recurrent tumours in 39 patients were included. The mean follow-up duration was 26.4 ± 13.7 months. Tumour volume decreased significantly from 0.20 ± 0.35 ml before ablation to 0.02 ± 0.11 ml (P < .001), with a mean volume reduction ratio of 95.1 ± 12.3 %. Fifty tumours (82.0 %) completely disappeared. Eleven tumours were visible at last follow-up US. The mean serum thyroglobulin level decreased from 1.21 ± 1.91 to 0.50 ± 0.80 ng/ml (P = .001). The overall complication rate was 7.7 % (3/39). RFA can effectively control locoregional recurrent PTC without life-threatening complications; therefore, RFA may replace “berry picking surgery” in selected patients. • RFA for recurrent PTC achieved a volume reduction ratio of 95.1 ± 12.3 % • Eighty-two percent (50/61) of recurrent PTC completely disappeared after RFA • The mean serum thyroglobulin level decreased significantly (P = .001) after RFA • RFA may replace “berry picking surgery” for recurrent PTC

CHEK2 mutations and the risk of papillary thyroid cancer.

Abstract: Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi-organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer-free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395 and I157T). We compared the family histories reported by patients with a CHEK2 mutation to those of non-carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%) unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%) age- and sex-matched controls (OR 3.3; p A, 1100delC or del5395) was associated with a higher risk of thyroid cancer (OR = 5.7; p = 0.006), than was the missense mutation I157T (OR = 2.8; p = 0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2 times more commonly than non-carriers (16.4% vs.8.1%; p = 0.05). A CHEK2 mutation was found in seven of 11 women (63%) with multiple primary cancers of the breast and thyroid (OR = 10; p = 0.0004). These results suggest that CHEK2 mutations predispose to thyroid cancer, familial aggregations of breast and thyroid cancer and to double primary cancers of the breast and thyroid.

Impact of Extent of Surgery on Survival for Papillary Thyroid Cancer Patients Younger Than 45 Years

Abstract: Context: Papillary thyroid cancer (PTC) patients 1.0 cm, regardless of age. Objective: Our objective was to examine the impact of extent of surgery on overall survival (OS) in patients <45 years old with stage I PTC of 1.1 to 4.0 cm. Design, Setting, and Patients: Adult patients <45 years of age undergoing surgery for stage I PTC were identified from the National Cancer Data Base (NCDB, 1998–2006) and the Surveillance, Epidemiology, and End Results dataset (SEER, 1988–2006). Main Outcome Measure: Multivariable modeling was used to compare OS for patients undergoing total thyroidectomy vs lobectomy. Results: In total, 29 522 patients in NCDB (3151 lobectomy, 26 371 total thyroidectomy) and 13 510 in SEER (1379 lobectomy, 12 131 total thyroidectomy) were included. Compared with patients undergoing lobectomy, patients having total thyroidectomy more often had extrathyroidal a...

Prognostic significance of extranodal extension of regional lymph node metastasis in papillary thyroid cancer

Abstract: © 2014 Wiley Periodicals, Inc. Head Neck 37: 1336-1343, 2015 © 2014 Wiley Periodicals, Inc. Background The presence and location of regional lymph node metastasis affect the prognosis of patients with thyroid cancer. Lymph node classification of the current TNM system may be inadequate because it insufficiently characterizes the nature and severity of lymph node metastasis that may influence prognosis. Methods We retrospectively studied 240 patients with papillary thyroid cancer and node metastases who had undergone total thyroidectomy, lymph node dissection, and postoperative 131I treatment at the University Cancer Center between 1994 and 2004. We reviewed the status of regional lymph node metastasis, including the location, number, largest size, and extranodal tumor extension and analyzed their effect on the prognosis of the patients. Results There were 172 women and 68 men, with a median age of 38 years and median tumor size of 1.9 cm. Thirty-five percent had only central compartment (N1a) nodal metastasis and 65% had involvement of both central and lateral compartments (N1b). There were a median of 4 nodes containing metastasis with a median largest diameter of 1.2 cm. Sixty patients (25%) had extranodal extension of cancer. Multivariate analysis showed that patient age (p = .0017; hazard ratio [HR], 2.156), >3 lymph node metastasis (p = .0316; HR, 1.806), and extranodal extension (p < .0001; HR, 4.027) were independent predictors of disease recurrence. Patient age (p = .0034; HR, 22.068), vascular invasion (p = .01; HR, 8.2), and extranodal extension (p = .022; HR, 12.597) were independent predictors of disease-specific survival (DSS). The DSS and recurrence-free survival curve between patients with and without extranodal extension differ significantly (p < .0001). For those older than 45 years, the 10-year recurrence was 11 of 43 patients for those without extranodal extension and 24 of 27 patients for those with extranodal extension (p < .001). Among patients with stage 4a/4b, those with extranodal extension had a significantly worse DSS and disease-free survival (DFS; p < .001) than those without extranodal extension. The prognosis of patients with stage 4a/4b cancer who had no extranodal extension was the same as patients with stage 3 cancer. The status of extranodal extension seems to be a stronger prognostic predictor than the location of metastatic lymph nodes (N1a/1b). Conclusion Presence of extranodal extension of metastatic nodes is a significant adverse independent prognostic factor for patients with lymph node metastasis from papillary cancer. This may need to be considered in future updates of the TNM system for thyroid cancer.

Current Understanding of BRAF Alterations in Diagnosis, Prognosis, and Therapeutic Targeting in Pediatric Low-Grade Gliomas

Abstract: The mitogen-activated protein kinase (MAPK) pathway is known to play a key role in the initiation and maintenance of many tumors as well as normal development. This often occurs through mutation of the genes encoding RAS and RAF proteins which are involved in signal transduction in this pathway. BRAF is one of three RAF kinases which act as downstream effectors of growth factor signaling leading to cell cycle progression, proliferation, and survival. Initially reported as a point mutation (V600E) in the majority of metastatic melanomas, other alterations in the BRAF gene have now been reported in a variety of human cancers including papillary thyroid cancer, colon carcinomas, hairy cell leukemia, and more recently in gliomas. The identification of oncogenic mutations in the BRAF gene have led to a revolution in the treatment of metastatic melanoma using targeted molecular therapies that affect the MAPK pathway either directly through BRAF inhibition or downstream through inhibition of MEK. This review describes the molecular biology of BRAF in the context of pediatric low-grade gliomas, the role of BRAF as a diagnostic marker, the prognostic implications of BRAF, and evidence for therapeutic targeting of BRAF.

Obesity and risk of thyroid cancer: evidence from a meta-analysis of 21 observational studies.

Abstract: Background Several studies have evaluated the association between obesity and thyroid cancer risk. However, the results remain uncertain. In this study, we conducted a meta-analysis to assess the association between obesity and thyroid cancer risk. Material/methods Published literature from PubMed, EMBASE, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) were retrieved before 10 August 2014. We included all studies that reported adjusted risk ratios (RRs), hazard ratios (HRs) or odds ratios (ORs), and 95% confidence intervals (CIs) of thyroid cancer risk. Results Thirty-two studies (n=12 620 676) were included in this meta-analysis. Obesity was associated with a significantly increased risk of thyroid cancer (adjusted RR=1.33; 95% CI, 1.24-1.42; I2=25%). In the subgroup analysis by study type, increased risk of thyroid cancer was found in cohort studies and case-control studies. In subgroup analysis by sex, both obese men and women were at significantly greater risk of thyroid cancer than non-obese subjects. When stratified by ethnicity, significantly elevated risk was observed in Caucasians and in Asians. In the age subgroup analysis, both young and old populations showed increased thyroid cancer risk. Subgroup analysis on smoking status showed that increased thyroid cancer risks were found in smokers and in non-smokers. In the histology subgroup analyses, increased risks of papillary thyroid cancer, follicular thyroid cancer, and anaplastic thyroid cancer were observed. However, obesity was associated with decreased risk of medullary thyroid cancer. Conclusions Our results indicate that obesity is associated with an increased thyroid cancer risk, except medullary thyroid cancer.

The RET oncogene in papillary thyroid carcinoma

Abstract: Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, accounting for greater than 80% of cases. Surgical resection, with or without postoperative radioiodine therapy, remains the standard of care for patients with PTC, and the prognosis is generally excellent with appropriate treatment. Despite this, significant numbers of patients will not respond to maximal surgical and medical therapy and ultimately will die from the disease. This mortality reflects an incomplete understanding of the oncogenic mechanisms that initiate, drive, and promote PTC. Nonetheless, significant insights into the pathologic subcellular events underlying PTC have been discovered over the last 2 decades, and this remains an area of significant research interest. Chromosomal rearrangements resulting in the expression of fusion proteins that involve the rearranged during transfection (RET) proto-oncogene were the first oncogenic events to be identified in PTC. Members of this fusion protein family (the RET/PTC family) appear to play an oncogenic role in approximately 20% of PTCs. Herein, the authors review the current understanding of the clinicopathologic role of RET/PTC fusion proteins in PTC development and progression and the molecular mechanisms by which RET/PTCs exert their oncogenic effects on the thyroid epithelium.

Long-term Results of Observation vs Prophylactic Selective Level VI Neck Dissection for Papillary Thyroid Carcinoma at a Cancer Center

Abstract: Importance The indication for prophylactic central neck dissection in papillary thyroid cancer (PTC) is controversial. Objective To compare long-term results of observation vs prophylactic selective level VI neck dissection for PTC. Design, Setting, and Participants We performed a retrospective cohort study of 812 patients with PTC who were treated from January 1, 1996, through January 1, 2007, at the Department of Head and Neck Surgery and Otorhinolaryngology of A. C. Camargo Cancer Center. A group of 580 consecutive patients with previously untreated PTCs and without lymph node metastasis were eligible for the study. We collected and analyzed retrospective data from February 1, 2012, through August 31, 2013. Interventions One hundred two patients (group A) underwent total thyroidectomy with elective central neck dissection; 478 patients (group B) underwent total thyroidectomy alone. Main Outcomes and Measures Absence of difference in rates of locoregional control and rates of major complications in group A. Results In group A, the rate of occult metastatic disease was 67.2%. Patients in group A exhibited higher rates of temporary hypocalcemia (46.1% vs 32.2%; P = .004) and permanent hypoparathyroidism (11.8% vs 2.3%; P P = .04) and permanent (5.9% vs 1.5%; P = .02) recurrent laryngeal nerve dysfunction in group A. The overall recurrence rate at level VI was 1.9%. Conclusions and Relevance Although the risk for occult lymph node metastasis reached 67.2% in a selected group of patients, elective central neck dissection for patients with PTC increased the risk for complications and did not contribute to a decrease in local recurrence rates.

Thyroid cancer incidence attributable to overdiagnosis in the United States 1981-2011.

Abstract: Papillary thyroid cancer incidence has increased in the United States from 1978 through 2011 for both men and women of all ages and races. Overdiagnosis is partially responsible for this trend, although its magnitude is uncertain. This study examines papillary thyroid cancer incidence according to stage at diagnosis and estimates the proportion of newly diagnosed tumors that are attributable to overdiagnosis. We analyzed stage specific trends in papillary thyroid cancer incidence, 1981-2011, using the Surveillance, Epidemiology and End Results national cancer registries. Yearly changes in early and late-stage thyroid cancer incidence were calculated. We estimate that the proportion of incident papillary thyroid cancers attributable to overdiagnosis in 2011 was 5.5 and 45.5% in men ages 20-49 and 50+ and 41.1 and 60.1% in women ages 20-49 and 50+, respectively. Overdiagnosis has resulted in an additional 82,000 incident papillary thyroid cancers that likely would never have caused any clinical symptoms. The detection of early-stage papillary thyroid cancer outpaced that of late-stage disease from 1981 through 2011, in part due to overdiagnosis. Further studies into the prevention, risk stratification and optimal treatment of papillary thyroid cancer are warranted in response to these trends.

Multiple functional variants in long-range enhancer elements contribute to the risk of SNP rs965513 in thyroid cancer

Abstract: The [A] allele of SNP rs965513 in 9q22 has been consistently shown to be highly associated with increased papillary thyroid cancer (PTC) risk with an odds ratio of ∼1.8 as determined by genome-wide association studies, yet the molecular mechanisms remain poorly understood. Previously, we noted that the expression of two genes in the region, forkhead box E1 (FOXE1) and PTC susceptibility candidate 2 (PTCSC2), is regulated by rs965513 in unaffected thyroid tissue, but the underlying mechanisms were not elucidated. Here, we fine-mapped the 9q22 region in PTC and controls and detected an ∼33-kb linkage disequilibrium block (containing the lead SNP rs965513) that significantly associates with PTC risk. Chromatin characteristics and regulatory element signatures in this block disclosed at least three regulatory elements functioning as enhancers. These enhancers harbor at least four SNPs (rs7864322, rs12352658, rs7847449, and rs10759944) that serve as functional variants. The variant genotypes are associated with differential enhancer activities and/or transcription factor binding activities. Using the chromosome conformation capture methodology, long-range looping interactions of these elements with the promoter region shared by FOXE1 and PTCSC2 in a human papillary thyroid carcinoma cell line (KTC-1) and unaffected thyroid tissue were found. Our results suggest that multiple variants coinherited with the lead SNP and located in long-range enhancers are involved in the transcriptional regulation of FOXE1 and PTCSC2 expression. These results explain the mechanism by which the risk allele of rs965513 predisposes to thyroid cancer.

Follicular cell-derived thyroid cancer

Abstract: Follicular cell-derived thyroid cancers are derived from the follicular cells in the thyroid gland, which secrete the iodine-containing thyroid hormones. Follicular cell-derived thyroid cancers can be classified into papillary thyroid cancer (80-85%), follicular thyroid cancer (10-15%), poorly differentiated thyroid cancer (<2%) and undifferentiated (anaplastic) thyroid cancer (<2%), and these have an excellent prognosis with the exception of undifferentiated thyroid cancer. The advent and expansion of advanced diagnostic techniques has driven and continues to drive the epidemic of occult papillary thyroid cancer, owing to overdiagnosis of clinically irrelevant nodules. This transformation of the thyroid cancer landscape at molecular and clinical levels calls for the modification of management strategies towards personalized medicine based on individual risk assessment to deliver the most effective but least aggressive treatment. In thyroid cancer surgery, for instance, injuries to structures outside the thyroid gland, such as the recurrent laryngeal nerve in 2-5% of surgeries or the parathyroid glands in 5-10% of surgeries, negatively affect quality of life more than loss of the expendable thyroid gland. Furthermore, the risks associated with radioiodine ablation may outweigh the risks of persistent or recurrent disease and disease-specific mortality. Improvement in the health-related quality of life of survivors of follicular cell-derived thyroid cancer, which is decreased despite the generally favourable outcome, hinges on early tumour detection and minimization of treatment-related sequelae. Future opportunities include more widespread adoption of molecular and clinical risk stratification and identification of actionable targets for individualized therapies.

MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer

Abstract: Despite low mortality rates, nodal recurrence in papillary thyroid carcinoma occurs in up to 20 % of patients. Emerging evidences indicate that dysregulated microRNAs are implicated in the process of metastasis. In the present study, we investigated whether miR-9, miR-10b, miR-21 and miR-146b levels are predictive of papillary thyroid carcinoma recurrence. Using macro-dissection followed by quantitative real-time PCR, we measured miR-9, miR-10b, miR-21 and miR-146b expression levels in formalin-fixed, paraffin-embedded samples of 66 patients with papillary thyroid carcinoma categorized into two groups: the recurrent group (n = 19) and the non-recurrent group (n = 47). All patients underwent total thyroidectomy and were followed for at least 120 months after surgery to be considered recurrence-free. Univariate and multivariate analysis were performed using the Cox proportional hazard model in order to identify associations between multiple clinical variables and microRNA expression levels and papillary thyroid carcinoma recurrence. MiR-9 and miR-21 expression levels were found to be significant prognostic factors for recurrence in patients with papillary thyroid carcinoma (HR = 1.48; 95 % CI 1.24-1.77, p < 0.001; and HR = 1.52; 95 % CI 1.18-1.94, p = 0.001; respectively). Multivariate analysis involving the expression level of miR-9 and miR-21 and various clinical parameters identified the expression of these microRNAs as independent prognostic factors for papillary thyroid cancer patients. In conclusion, our results support the potential clinical value of miR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid carcinoma.

MicroRNA Expression and Association with Clinicopathologic Features in Papillary Thyroid Cancer: A Systematic Review.

Abstract: Background: Studies have suggested that microRNAs (miR) may be useful prognostic markers and are associated with aggressive clinicopathologic features in papillary thyroid cancer (PTC). This systematic review examined associations between miRs and aggressive clinicopathologic features in PTC. Methods: A literature search was performed within the PubMed, Embase, Cochrane, Web of Science, and Scopus databases for papers published prior to November 24, 2014. The search was performed by combining the concepts “thyroid tumor” with “microRNA” and by using “and” as the Boolean operator. Upon retrieval of candidate studies, full-text publications were reviewed in their entirety and selected if they examined the prognostic significance between miR expression and established aggressive clinicopathologic features of PTC. Results: Fifteen studies from 13 unique groups that included 807 patients were reviewed. Most of the studies were retrospective, and none included patients who had undergone routine central lymph no...

Estrogen Receptor α Induces Prosurvival Autophagy in Papillary Thyroid Cancer via Stimulating Reactive Oxygen Species and Extracellular Signal Regulated Kinases

Abstract: Context: The incidence of papillary thyroid cancer (PTC) shows a predominance in females, with a male:female ratio of 1:3, and none of the known risk factors are associated with gender difference. Increasing evidence indicates a role of estrogen in thyroid tumorigenesis, but the mechanism involved remains largely unknown. Objective: This study aimed to assess the contribution of autophagy to estrogen receptor α (ERα)-mediated growth of PTC. Design: The expression of ERα in thyroid tissue of patients with PTC tissues was analyzed. Cell viability, proliferation, and apoptosis were evaluated after chemical and genetic inhibition of autophagy. Autophagy in PTC cell lines BCPAP and BCPAP-ERα was assessed. Results: ERα expression was increased in PTC tissues compared with the adjacent nontumor tissues. Estrogen induced autophagy in an ERα-dependent manner. Autophagy induced by estrogen/ERα is associated with generation of reactive oxygen species, activation of ERK1/2, and the survival/growth of PTC cells. Chemi...

Impact of estrogen and progesterone receptor expression on the clinical and molecular features of papillary thyroid cancer

Abstract: Background Thyroid cancer is highly prevalent in women during the fertile age, which suggests a possible impact of hormonal and reproductive factors. Methods We studied the expression of estrogen receptor α (ERα or ESR1) and progesterone receptor (PR or PGR) in 182 female and male patients with papillary thyroid cancer and correlated it to clinical and molecular features. Results ERα and PR expression was found in 66.5 and 75.8% of patients respectively and was significantly correlated with larger tumor size and with a non-incidental diagnosis. Moreover, a trend toward a higher prevalence of local metastases was observed in ER- and PR-expressing tumors, which possibly indicates a more aggressive behavior. Interestingly, the occurrence of the 'receptor conversion' phenomenon, which has already been reported to have a negative prognostic effect in breast cancer, was demonstrated for the first time in thyroid tumors. Indeed, almost all of the ERα-positive primary tumors analyzed had ERα-negative metastatic lymph nodes. At the genetic analyses, BRAF(V600E) mutation was detected in 23.2% of the tumors and had a higher prevalence in larger tumors and in those with a stronger ERα or PR staining. Conclusions The whole of the findings reported in the present study argue for an association between ERα and PR sex hormone receptor expression and a more aggressive presentation. Although no impact on outcome was found, the evaluation of ERα and PR receptor expression could add insights into the biological behavior of tumors and could modify the follow-up, particularly in fertile women affected with persistent disease.