Familial non-medullary thyroid cancer: a critical review.

BACKGROUND: Familial non-medullary thyroid carcinoma (FNMTC), mainly of papillary histotype (FPTC), is defined by the presence of the disease in two or more first-degree relatives in the absence of other known familial syndromes. With the increasing incidence of PTC in the recent years, the familial form of the disease has also become more common than previously reported and constitutes nearly 10% of all thyroid cancers. Many aspects of FNMTC are debated, concerning both clinical and genetic aspects. Several studies reported that, in comparison with sporadic PTCs, FPTCs are more aggressive at disease presentation, while other authors reported no differences in the clinical behavior of sporadic and familial PTCs. For this reason, recent guidelines do not recommend screening of family members of patients with diagnosis of differentiated thyroid cancer (DTC). FNMTC is described as a polygenic disorder associated with multiple low- to moderate-penetrance susceptibility genes and incomplete penetrance. At the moment, the genetic factors contributing to the development of FNMTC remain poorly understood, though many putative genes have been proposed in the recent years. PURPOSE: Based on current literature and our experience with FNMTC, in this review, we critically discussed the most relevant controversies, including its definition, the genetic background and some clinical aspects as screening and treatment.

Identification of topological features in renal tumor microenvironment associated with patient survival.

Motivation: As a highly heterogeneous disease, the progression of tumor is not only achieved by unlimited growth of the tumor cells, but also supported, stimulated, and nurtured by the microenvironment around it. However, traditional qualitative and/or semi-quantitative parameters obtained by pathologist's visual examination have very limited capability to capture this interaction between tumor and its microenvironment. With the advent of digital pathology, computerized image analysis may provide a better tumor characterization and give new insights into this problem. Results: We propose a novel bioimage informatics pipeline for automatically characterizing the topological organization of different cell patterns in the tumor microenvironment. We apply this pipeline to the only publicly available large histopathology image dataset for a cohort of 190 patients with papillary renal cell carcinoma obtained from The Cancer Genome Atlas project. Experimental results show that the proposed topological features can successfully stratify early- and middle-stage patients with distinct survival, and show superior performance to traditional clinical features and cellular morphological and intensity features. The proposed features not only provide new insights into the topological organizations of cancers, but also can be integrated with genomic data in future studies to develop new integrative biomarkers. Availability and implementation: https://github.com/chengjun583/KIRP-topological-features. Contact: 1271992826@qq.com or kunhuang@iu.edu. Supplementary information: Supplementary data are available at Bioinformatics online.

Effects of different extracts of curcumin on TPC1 papillary thyroid cancer cell line.

BACKGROUND: The thyroid gland is one of the largest endocrine glands in the body. The vast majority of TCs (> 90%) originate from follicular cells and are defined as differentiated thyroid cancers (DTC) and the two histological subtypes are the papillary TC with its variants and the follicular TC. Curcumin possesses a wide variety of biological functions, and thanks to its properties, it has gained considerable attention due to its profound medicinal values (Prasad, Gupta, Tyagi, and Aggarwal, Biotechnol Adv 32:1053-1064, 2014). We have undertaken the present work in order to define the possible role of curcumin in modulating the genetic expression of cell markers and to understand the effectiveness of this nutraceutical in modulating the regression of cancer phenotype. METHODS: As a template we used the TPC-1 cells treated with the different extracts of turmeric, and examined the levels of expression of different markers (proliferative, inflammatory, antioxidant, apoptotic). RESULTS: Treatment with the three different curcumin extracts displays anti-inflammatory, antioxidant properties and it is able to influence cell cycle with slightly different effects upon the extracts. Furthermore curcumin is able to influence cell metabolic activity vitality. CONCLUSIONS: In conclusion curcumin has the potential to be developed as a safe therapeutic but further studies are needed to verify its antitumor ability in vivo.

Outcome and characteristics of patients with malignant pleural effusion from differentiated thyroid carcinoma.

Metastatic differentiated thyroid carcinoma (DTC) is an uncommon cause of malignant pleural effusion (MPE) and the characteristics and clinical course have been rarely described. Herein, we report a retrospective review of the clinical course of 18 patients (15 women and 3 men) with MPE from DTC who underwent treatment at our institution between January 2005 and December 2014. MPE from DTC was diagnosed based on cytology and/or level of thyroglobulin in the pleural fluid. Pathologically, papillary carcinoma was found in 16 patients and follicular carcinoma in 2 patients. Median ages at initial diagnosis of DTC and MPE were 64 years (range, 22-79) and 74 years (range, 39-86), respectively. All patients showed radiologically apparent lung metastases, with MPE developing after 0-212 months (median, 25). In 16 patients (88.9%), other coexistent distant metastases at the time of MPE diagnosis were found in the bone (n = 10), brain (n = 5), and skin (n = 2). All patients were treated conservatively with palliative thoracentesis or chest tube drainage with or without pleurodesis. Recurrent MPE after treatment was seen in 9 patients; discharge to home health care after treatment for MPE was possible for 14 patients. The overall survival after initial diagnosis varied considerably from 14 months to 37 years, but the median survival after appearance of MPE was 10 months (range, 1-28). Systemic therapy for iodine-resistant recurrent thyroid disease may need to be considered as a treatment option for patients with MPE.

Renal Function is Associated with Nephrometry Score After Partial Nephrectomy: A Study Using Diethylene Triamine Penta-Acetic Acid (DTPA) Renal Scanning.

PURPOSE: The aim of this study was to evaluate the effect of renal tumor anatomical characteristics on renal function change after partial nephrectomy using the scoring systems and the glomerular filtration rate (GFR) estimated from diethylene triamine penta-acetic acid (DTPA) scans. METHODS: Patients who underwent DTPA renal scans before and after partial nephrectomy from January 2009 to December 2011 were identified retrospectively. The anatomical characteristics of renal tumors were standardized using the RENAL, PADUA and C-index scoring systems. Associations between scoring systems and change in GFRs were evaluated using a correlation coefficient. Predictors of GFR change and postoperative new-onset chronic kidney disease (CKD) after partial nephrectomy were assessed. RESULTS: A total of 185 patients with a mean tumor size of 2.6 cm (median 2.3, range 0.5-10) were identified. Mean ischemia time was 21.5 min. The last DTPA renal scan was performed at a mean follow-up duration of 23.3 months after surgery, and the mean decrease in GFR was 8.1 ml/min. By multivariable analysis, preoperative GFR (ß = -039; p < 0.001), RENAL complexity score (ß = -5.32; p < 0.001), and C-index complexity (ß = -5.19; p < 0.001) were independent predictors of decreased GFR on DTPA. Of 175 patients in whom preoperative estimated GFR (eGFR) was > 60 ml/min/1.73 m(2), CKD developed in 14 (8 %) patients after surgery. Independent factors predicting new-onset CKD were preoperative eGFR (odds ratio [OR] 0.91; p = 0.047), age (OR 1.13; p = 0.003), and diabetes (OR 5.10; p = 0.038). CONCLUSIONS: Although each scoring system describing the complexity of renal tumors correlates with change in GFR after partial nephrectomy, RENAL and C-index score were significantly predictive of GFR reduction.

Increased risk of papillary thyroid cancer related to hormonal factors in women.

Strikingly higher rates of papillary thyroid cancer in women compared with men suggest that hormonal factors may be involved in the development of this cancer. A number of independent studies have investigated the association between hormonal factors and papillary thyroid cancer risk in women but yielded conflicting and inconclusive findings. We performed a meta-analysis of all currently published studies to provide better estimates for the risk of papillary thyroid cancer related to menstrual, reproductive, and other hormonal factors in women. Six cohort studies and three case-control ones were included into our study after a comprehensive literature search. The pooled relative risk (RR) with 95 % confidence interval (95 % CI) implicated that late age at menopause was associated with an increased risk of papillary thyroid cancer (RR = 1.39, 95 % CI 1.03-1.89, P = 0.032). No significant association was demonstrated between papillary thyroid cancer risk and other hormone-related factors, including oral contraceptive, hormone replacement therapy, age at menarche, parity, age at first birth, menopausal status, and breast feeding. Subgroup analysis by study design confirmed those associations. Sensitivity analysis did not materially alter the pooled results. The meta-analysis firstly suggests that late age at menopause is a risk factor for papillary thyroid cancer.

Clinicopathologic Analysis of Micropapillary Urothelial Carcinoma of the Upper Urinary Tract: Implications for HER2-Targeted Therapy.

Introduction/Background To determine the clinical significance of micropapillary urothelial carcinoma (MPUC) of the upper urinary tract (UTUC) and a potential therapeutic strategy. Patients and Methods A retrospective cohort study was conducted to examine the incidence of micropapillary UTUC from 2010 to 2018 and its clinicopathological characteristics. Clinical outcomes and cancer-specific survival (CSS) were compared between MPUC and conventional UTUC matched by stage within a 6-month variation of receiving surgery. Results A total of 24 MPUC cases were identified out of 901 cases (2.7%) of urothelial carcinoma (UC) of the renal pelvis and ureter. MPUC was significantly smaller (<3 cm) and associated with nodal metastasis compared with conventional UTUC (P = .017 & 0.021, respectively); however, no significant difference was observed for lymphovascular invasion, distant metastasis, or CSS (P > 0.50, respectively) compared with match controls. Six MPUC patients (25%) developed metastasis to the liver, lymph nodes, and lung during follow-up. Patients with HER2-positive MPUC (3 of 4) had a significantly higher risk of metastasis compared with HER2-negative MPUC (3 of 20; P = 0.035). Conclusions MPUC is an aggressive variant of UTUC and usually presents as a small locally advanced disease. HER2 immunohistochemistry may identify the subset of patients with micropapillary UTUC that are candidates for targeted therapy.

The prognostic roles of the prognostic nutritional index in patients with intraductal papillary mucinous neoplasm.

The preoperative accurate diagnosis is difficult in the patients with intraductal papillary mucinous neoplasm (IPMN). The aim of the present study was to elucidate the roles of systemic inflammation responses and nutritional status indexes in IPMN. High-grade dysplasia was classified as a malignant neoplasm in the study. We retrospectively reviewed 155 patients who underwent pancreatectomy. The correlation between the clinical factors and several indexes of a systemic inflammation response and nutritional status was analyzed. Among the biomarkers, prognostic nutritional index (PNI) value of malignant IPMN patients was significantly lower than that of benign IPMN patients (P = 0.023), whereas PNI was not significant predictor for malignant IPMN. The multivariate analysis showed that a PNI < 43.5 (odds ratio [OR] 16.1, 95% CI 1.88-138.5, P = 0.011) and a carbohydrate antigen (CA) 19-9 level > 22.5 U/mL (OR 6.64, 95% CI 1.73-25.6, P = 0.006) were significant independent predictors of the presence of lymph node metastasis (LNM). Our scoring system developed based on these two factors. Patients with a score of 0 had no LNM and zero disease-related death. The present study suggested the roles of PNI on the IPMN patients who undergo curative pancreatectomy.

Ectopic Thyroid Papillary Carcinoma with Cervical Lymph Node Metastasis as the Initial Presentation, Accompanied by Benign Thyroid Gland.

BACKGROUND: Ectopic thyroid papillary carcinoma presenting as bilateral neck lymph nodes metastasis is very rare. Ectopic thyroid tissue may appear in any location along the trajectory of the thyroglossal duct from the foramen cecum to the mediastinum. It is subject to malignant transformation and is classically accompanied by a similar transformation of the native thyroid gland. Similar to that of the native thyroid gland, the most common malignancy found is Papillary thyroid carcinoma. Unusual cases in which ectopic thyroid carcinoma presents with normal native tissue support an alternative hypothesis that ectopic thyroid tissue may develop malignancies independently from the native thyroid gland. OBJECTIVE: We present an extremely rare case of a 30-year-old woman previously diagnosed with Hashimoto's thyroiditis, presenting with a palpable mass in the lateral neck suspicious for malignancy. RESULTS: After several examinations and surgical removal of the mass, histopathologic evaluation of the continuous sections of the thyroid, demonstrated metastatic disease from papillary carcinoma of the thyroid. Total thyroidectomy and biopsy revealed benign thyroid tissue without any foci of microcarcinoma. A hypothesis of ectopic thyroid tissue and its malignant transformation was made. CONCLUSION: By presenting this case, our goal is to highlight and make the physicians aware of the possibility of developing primary carcinoma of the ectopic thyroid tissue, without an active tumor of the thyroid gland.

Should Contralateral Nodules Be an Indication of Total or Completion Thyroidectomy for Patients With Unilateral Papillary Thyroid Carcinoma?

Objective: To determine whether papillary thyroid carcinoma (PTC) patients with benign or nonsuspicious nodules in the contralateral lobe have a higher rate of recurrence or worse survival after lobectomy compared to those without nodules in the contralateral lobe. Methods: Adult patients who underwent lobectomy and were diagnosed with unilateral PTC (2013-2015), were identified from an institutional database. Patients who previously had cytologically benign nodules or nonsuspicious nodules in the contralateral lobe comprised the contralateral nodule (CN) group. Patients who did not have nodules in the contralateral lobe comprised the unilateral nodule (UN) group. Results: 370 patients were included: 242 in the UN group and 128 in the CN group. After a median follow-up of 62 months (range, 16-85 months), recurrence was confirmed in 4.1% patients in the UN group and 5.5% patients in the CN group (p = 0.559). Clinical contralateral lobe PTC was detected in 2.9% (7/242) of patients from the UN group and 3.9% (5/128) of patients from the CN group (p = 0.601). The 5-year contralateral lobe recurrence-free survival (RFS) rates were 96.8% in the UN group and 97.4% in the CN group (p = 0.396). The 5-year loco-regional RFS rates were 98.4% in the UN group and 97.8% in the CN group (p = 0.690). The 5-year disease-specific survival rates were both 100%. Conclusion: PTC patients with benign or nonsuspicious CNs have similar recurrence and survival rates after lobectomy compared to those without CNs. CNs alone should not be an indication for total or completion thyroidectomy.

P-wave dispersion in endogenous and exogenous subclinical hyperthyroidism.

BACKGROUND: The aim of this study was to measure maximum P wave duration (Pmax) and P wave dispersion (PWD), which can be indicators for the risk of paroxysmal atrial fibrillation when increased, and to reveal their relationship with thyroid hormone levels in patients with endogenous and exogenous subclinical hyperthyroidism. METHODS: Seventy-one patients with sublinical thyrotoxicosis (34 endogenous, 37 exogenous) and 69 healthy individuals were enrolled in the study. Pmax and minimum P wave duration (Pmin) on electrocardiogram recordings were measured and PWD was calculated as Pmax-Pmin. RESULTS: Pmax (p<0.001) and PWD (p<0.001) values were significantly higher in patients with endogenous subclinical hyperthyroidism compared with the control group. Pmax (p<0.001) and PWD (p<0.001) values were significantly higher in patients with exogenous subclinical thyrotoxicosis compared with the control group. Pmax (p=0.710) and PWD (p=0.127) were not significantly different in patients with endogenous subclinical hyperthyroidism compared with exogenous subclinical hyperthyroid patients. Pmax and PWD negatively associated with TSH in endogenous and exogenous subclinical hyperthyroidism. CONCLUSION: In the present study, we observed that Pmax and PWD were longer in patients with endogenous and exogenous subclinical hyperthyroidism. Lack of a difference in Pmax and PWD between patients with endogenous and exogenous subclinical hyperthyroidism seems to support the idea that hormone levels rather than the etiology of thyrotoxicosis affect the heart.

Quality of Life in Patients with Papillary Thyroid Microcarcinoma According to Treatment: Total Thyroidectomy with or without Radioactive Iodine Ablation.

BACKGROUND: Recently, there has been some controversy regarding the role of radioactive iodine (RAI) ablation in the treatment of low-risk differentiated thyroid carcinoma (DTC), especially papillary thyroid microcarcinoma (PTMC). This study aimed to compare quality of life (QoL) parameters between patients with PTMC who underwent total thyroidectomy (TT) alone and those who underwent TT with RAI ablation. METHODS: In this cross-sectional study, patients with PTMC who underwent TT with/without RAI remnant ablation were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: the 12-item short-form health survey (SF-12), thyroid cancer-specific quality of life (THYCA-QoL) questionnaire, and fear of progression (FoP) questionnaire. RESULTS: The TT and TT with RAI groups comprised 107 and 182 patients, respectively. The TT with RAI group had significantly lower serum thyrotropin (TSH) levels than the TT group. However, after matching for TSH levels between the groups (n=100 in both groups), there were no significant differences in baseline characteristics. According to the SF-12, the score for general health was significantly lower in the TT with RAI group than in the TT group (P=0.047). The THYCA-QoL also showed a significant difference in the "felt chilly" score between groups (P=0.023). No significant differences in FoP scores were observed between the groups. CONCLUSION: Patients with PTMC who underwent TT with RAI ablation experienced more health-related problems than those managed with TT alone. These findings support the idea that RAI ablation should be carefully considered in patients with low-risk DTCs.

Papillary Thyroid Cancer-Aggressive Variants and Impact on Management: A Narrative Review.

INTRODUCTION: Aggressive variants of papillary thyroid cancer (PTC) have been described with increasing frequency. These variants include diffuse sclerosing variant, tall cell variant, columnar cell variant, solid variant, and hobnail variant. METHODS: We have performed a review of the more aggressive variants of PTC with respect to main characteristics, histological and molecular features, and the consequences that the knowledge of these variants should have in the treatment of the patients. RESULTS: At the present time, we do not know the prognostic value of these aggressive PTC variants. The extent of the surgical treatment and adjuvant therapy necessary should be decided on the basis of the extent of the tumor at presentation and the opinion of experienced clinicians. CONCLUSION: These aggressive variants should be known by clinicians, to avoid underdiagnosis, and treated according to the latest recommendations in the literature.

Stabilization of beta-catenin induces pancreas tumor formation.

BACKGROUND & AIMS: beta-Catenin signaling within the canonical Wnt pathway is essential for pancreas development. However, the pathway is normally down-regulated in the adult organ. Increased cytoplasmic and nuclear localization of beta-catenin can be detected in nearly all human solid pseudopapillary neoplasms (SPN), a rare tumor with low malignant potential. Conversely, pancreatic ductal adenocarcinoma (PDA) accounts for the majority of pancreatic tumors and is among the leading causes of cancer death. Whereas activating mutations within beta-catenin and other members of the canonical Wnt pathway are rare, recent reports have implicated Wnt signaling in the development and progression of human PDA. Here, we sought to address the role of beta-catenin signaling in pancreas tumorigenesis. METHODS: Using Cre/lox technology, we conditionally activated beta-catenin in a subset of murine pancreatic cells in vivo. RESULTS: Activation of beta-catenin results in the formation of large pancreatic tumors at a high frequency in adult mice. These tumors resemble human SPN based on morphologic and immunohistochemical comparisons. Interestingly, stabilization of beta-catenin blocks the formation of pancreatic intraepithelial neoplasia (PanIN) in the presence of an activating mutation in Kras that is known to predispose individuals to PDA. Instead, mice in which beta-catenin and Kras are concurrently activated develop distinct ductal neoplasms that do not resemble PanIN lesions. CONCLUSIONS: These results demonstrate that activation of beta-catenin is sufficient to induce pancreas tumorigenesis. Moreover, they indicate that the sequence in which oncogenic mutations are acquired has profound consequences on the phenotype of the resulting tumor.

Differential expression of CK 19 in follicular adenoma, well-differentiated tumour of uncertain malignant potential (WDT-UMP) and follicular variant of papillary carcinoma.

OBJECTIVE: To see the expression of cytokeratin 19, a proven helpful marker for the differential diagnosis of neoplastic follicular patterned lesions of thyroid. METHODS: This was a retrospective study carried out in the Department of Pathology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi from 2000 to 2005. The haematoxylin and eosin (H&E) stained sections were reviewed and the cases were classified according to already published criteria. On the basis of the recent recommendations by Chemobyl Pathologists Group, encapsulated follicular patterned lesions with questionable nuclear changes were categorized as well - differentiated tumours of uncertain malignant potential (WDT-UMP). Formalin fixed paraffin embedded tissues of follicular adenoma, WDT-UMP and follicular variant of papillary carcinoma were obtained for CK 19 immunostaining. RESULTS: All (16) cases of follicular adenoma were negative for CK19. In a total of 35 cases of WDT- UMP, 10 cases scored 3+ positive for CK19, 15 were 2+ positive and remaining 10 cases were 1+ positive. There were 43 cases of follicular variant of papillary carcinoma with 4+ CK 19 positivity, 14 were 3+ positive and 3 were 2+ positive. CONCLUSION: CK19 is a good and useful diagnostic marker for differential diagnosis of follicular adenoma, WDT-UMP and follicular variant of papillary carcinoma. The recommendations by Chornobyl Pathologists Group need to be adopted and the cases of WDT-UMP require strict follow-up.

Localization and characterization of thyroid microcalcifications: A histopathological study.

Thyroid calcification is frequent in thyroid nodules. The aim of our study was to evaluate the prevalence of calcifications in thyroid tissue samples of patients with various thyroid diseases, and to identify their composition according to their localization. Among 50 thyroid samples included, 56% were malignant (papillary carcinoma) and 44% were benign (adenoma, multinodular goiter, Graves' disease, sarcoidosis). Calcifications were found in 95% of samples using polarised light microscopy, whereas only 12% were described in initial pathological reports. Three types were individualised and analyzed by infrared spectrometry (µFTIR): colloid calcifications composed of calcium oxalate, capsular calcifications and psammoma bodies, both composed of calcium phosphate. Of notice, psammoma bodies characterized by FE-SEM were composed of concentric structure suggesting a slow process for crystal deposition. Calcium phosphates were found only in malignant samples whereas calcium oxalate was not associated with a define pathology. Proliferation assessed by KI67 staining was high (33% of positive follicles), and RUNX2, OPN, and CD44 positive staining were detected in thyrocytes with a broad variation between samples. However, thyrocyte proliferation and differentiation markers were not associated with the number of crystals. TRPV5 and CaSR expression was also detected in thyrocytes. mRNA transcripts expression was confirmed in a subgroup of 10 patients, altogether with other calcium transporters such as PMCA1 or Cav1.3. Interestingly, TRPV5 mRNA expression was significantly associated with number of colloid calcifications (rho = -0.72; p = 0.02). The high prevalence of calcium oxalate crystals within colloid gel raises intriguing issues upon follicle physiology for calcium and oxalate transport.

Longitudinal Assessment of Quality of Life According to Treatment Options in Low-Risk Papillary Thyroid Microcarcinoma Patients: Active Surveillance or Immediate Surgery (Interim Analysis of MAeSTro).

Background: In this ongoing multicenter prospective cohort study on active surveillance (AS) in low-risk papillary thyroid microcarcinoma (PTMC), we aimed to compare the quality of life (QoL) of participants based on their choice of treatment, that is, AS or immediate surgery (OP). Methods: QoL of 203 participants who chose AS and 192 participants who underwent OP was evaluated using a thyroid-specific QoL questionnaire at diagnosis and during follow-up (median 8 months). Results: The mean ages of the participants in the AS and OP groups were 47.3 ± 11.7 and 45.6 ± 10.5 years (p = 0.138), respectively, and the mean tumor sizes were 5.7 ± 1.6 and 6.5 ± 2.1 mm (p = 0.065), respectively. At baseline, significantly better psychological health (7.1 ± 1.3 vs. 6.8 ± 1.6, p = 0.023) and overall health (6.8 ± 1.2 vs. 6.5 ± 1.3, p = 0.018) were observed in the AS group than in the OP group. During follow-up, significantly better physical (7.9 ± 1.1 vs. 7.4 ± 1.2, p < 0.001), psychological (7.4 ± 1.3 vs. 6.9 ± 1.6, p = 0.004), and overall health (6.9 ± 1.0 vs. 6.5 ± 1.1, p = 0.002) were observed in the AS group than in the OP group, whereas spiritual health was comparable between the two groups. Compared with the AS group, the OP group experienced more fatigue, changes in voice and appearance, less satisfaction, and low fear of recurrence. The self-assessed financial burden was similar at baseline and follow-up in both groups. Conclusion: The QoL of PTMC patients is different according to the type of treatment. Better psychological health at baseline and physical and psychological health at follow-up were observed in the AS group than in the OP group. However, studies with longer follow-up periods are needed.

Quality of Life in Patients with Papillary Thyroid Microcarcinoma Managed by Active Surveillance or Lobectomy: A Cross-Sectional Study.

Background: Active surveillance (AS) is recommended as an alternative to immediate surgery in patients with papillary thyroid microcarcinoma (PTMC), but the impact of AS on quality of life has not been reported. The aim of this study was to compare quality-of-life parameters in patients with PTMC under AS versus those who underwent lobectomy (LB). Methods: In this cross-sectional study, patients with PTMC were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: the 12-item short-form health survey, thyroid cancer-specific quality of life, and fear of progression. The results were compared after adjusting for age, sex, and serum thyrotropin levels. Results: The AS group comprised 43 patients, and the LB group comprised 148 patients. According to the 12-item short-form health survey questionnaire, the score for role limitations due to emotional problems showed a significant negative association between the groups (coefficient [coef]: -7.71 [confidence interval (CI) -15.26 to -0.16], p = 0.045). The thyroid cancer-specific quality of life questionnaire also showed statistically significant differences between the groups with respect to three scores: neuromuscular problems (coef: 4.99 [CI 0.63-10.62], p = 0.020), throat/mouth problems (coef: 5.28 [CI 0.18-10.38], p = 0.043), and scar problems (coef: 9.34 [CI 4.38-14.29], p < 0.001), suggesting a higher level of complaint in the LB group than in the AS group. No significant differences in fear of progression scores were seen between the two groups. Conclusions: Patients with PTMC underwent LB experienced more health-related problems than those managed by AS. These findings support the role of AS as a reasonable management option for patients with PTMC.

Gene expression in RET/PTC3 and E7 transgenic mouse thyroids: RET/PTC3 but not E7 tumors are partial and transient models of human papillary thyroid cancers.

We studied gene expression profiles in two mouse models of human thyroid carcinoma: the Tg-RET/PTC3 (RP3) and Tg-E7 mice. RP3 fusion gene is the most frequent mutation found in the first wave post-Chernobyl papillary thyroid cancers (PTCs). E7 is an oncoprotein derived from the human papillomavirus 16 responsible for most cervical carcinoma in women. Both transgenic mice develop thyroid hyperplasia followed by solid differentiated carcinoma in older animals. To understand the different steps leading to carcinoma, we analyzed thyroid gene expression in both strains at different ages by microarray technology. Important biological processes were differentially regulated in the two tumor types. In E7 thyroids, cell cycle was the most up-regulated process, an observation consistent with the huge size of these tumors. In RP3 thyroids, contrary to E7 tumors, several human PTC characteristics were observed: overexpression of many immune-related genes, regulation of human PTC markers, up-regulation of EGF-like growth factors and significant regulation of angiogenesis and extracellular matrix remodeling-related genes. However, similarities were incomplete; they did not concern the overall gene expression and were not conserved in old animals. Therefore, RP3 tumors are partial and transient models of human PTC. They constitute a good model, especially in young animals, to study the respective role of the biological processes shared with human PTC and will allow testing drugs targeting these validated variables.

Increased P2X7 receptor expression and function in thyroid papillary cancer: a new potential marker of the disease?

Nucleotides are increasingly recognized as nonredundant extracellular signals for chemotaxis, cell growth, and cytokine release. Effects of extracellular nucleotides are mediated by P2 receptors, among which the P2X(7) subtype is attracting increasing attention for its involvement in apoptosis, cell growth, and cytokine release. Recent studies showed that P2X(7) is overexpressed in chronic lymphocytic leukemia and breast and prostate cancer. The aim of the present study was to better understand the clinical significance of P2X(7) receptor expression in normal and cancer human thyroid tissues. P2X(7) receptor message and protein expression and functional activity were tested in two cell lines (FB1 and FB2) established from either anaplastic or papillary primary thyroid cancer and in several histological samples of human papillary cancer. We show here that human thyroid papillary carcinoma, whether of the classical or follicular variant, expresses the P2X(7) receptor (P2X(7)R) to a much higher level than normal thyroid tissue. The P2X(7)R was similarly up-regulated in FB1 and FB2 cell lines. In contrast to normal thyroid cells, both cell lines responded to extracellular nucleotide stimulation with a large increase in intracellular Ca(2+) and secretion of IL-6. Ca(2+) increase was attenuated and release of IL-6 was fully blocked by P2X(7)R inhibitors. Finally, the thyroid carcinoma cell lines had at least a 3-fold higher intracellular ATP concentration and maintained at least a 3-fold higher extracellular ATP level, compared with control cells. These data suggest that an enhanced P2X(7)R function might be a feature of human thyroid cancer.