Joint use of epidemiological and hospital medico-administrative data to estimate prevalence. Application to French data on breast cancer

Background Estimate complete, limited-duration, and hospital prevalence of breast cancer in a French Département covered by a population-based cancer registry and in whole France using complementary information sources. Methods: Incidence data from a cancer registry, national incidence estimations for France, mortality data, and hospital medico-administrative data were used to estimate the three prevalence indices. The methods included a modelling of epidemiological data and a specific process of data extraction from medico-administrative databases. Results: Limited-duration prevalence at 33 years was a proxy for complete prevalence only in patients aged less than 70 years. In 2007 and in women older than 15 years, the limited-duration prevalence at 33 years rate per 100,000 women was estimated at 2372 for Département Isère and 2354 for whole France. The latter rate corresponded to 613,000 women. The highest rate corresponded to women aged 65–74 years (6161 per 100,000 in whole France). About one third of the 33-year limited-duration prevalence cases were diagnosed five years before and about one fourth were hospitalized for breast-cancer-related care (i.e., hospital prevalence). In 2007, the rate of hospitalized women was 557 per 100,000 in whole France. Among the 120,310 women hospitalized for breast-cancer-related care in 2007, about 13% were diagnosed before 2004. Conclusion: Limited-duration prevalence (long- and short-term), and hospital prevalence are complementary indices of cancer prevalence. Their efficient direct or indirect estimations are essential to reflect the burden of the disease and forecast median- and long-term medical, economic, and social patient needs, especially after the initial treatment.     

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: The Increasing Incidence of Thyroid Cancer

Objective: (1) Describe current epidemiology of thyroid cancer in the United States; (2) evaluate hypothesized causes of the increased incidence of thyroid cancer; and (3) suggest next steps in research and clinical action.Methods: Analysis of data from Surveillance, Epidemiology and End Results System and the National Center for Vital Statistics. Literature review of published English-language articles through December 31, 2013.Results: The incidence of thyroid cancer has tripled over the past 30 years, whereas mortality is stable. The increase is mainly comprised of smaller tumors. These facts together suggest the major reason for the increased incidence is detection of subclinical, nonlethal disease. This has likely occurred through: health care system access, incidental detection on imaging, more frequent biopsy, greater volumes of and extent of surgery, and changes in pathology practices. Because larger-size tumors have increased in incidence also, it is possible that there is a concomitant true rise in thyroid cancer incidence. The only clearly identifiable contributor is radiation exposure, which has likely resulted in a few additional cases annually. The contribution of the following causes to the increasing incidence is unclear: iodine excess or insufficiency, diabetes and obesity, and molecular disruptions. The following mechanisms do not currently have strong evidence to support a link with the development of thyroid cancer: estrogen, dietary nitrate, and autoimmune thyroid disease.Conclusion: Research should focus on illuminating which thyroid cancers need treatment. Patients should be advised of the benefits as well as harms that can occur with treatment of incidentally identified, small, asymptomatic thyroid cancers.Abbreviations: BMI = body mass index CT = computed tomography SEER = Surveillance, Epidemiology, and End Results     

Metformin Reduces Thyroid Cancer Risk in Taiwanese Patients with Type 2 Diabetes

Background

Whether metformin may affect thyroid cancer risk has not been studied. This study investigated the association between metformin use and thyroid cancer risk in Taiwanese patients with type 2 diabetes mellitus.

Methods

The reimbursement databases of all diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and 1,414,723 patients with type 2 diabetes were followed for thyroid cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of metformin exposure using tertile cutoffs for cumulative duration of therapy and cumulative dose were calculated and adjusted hazard ratios were estimated by Cox regression. Additional sensitivity analyses were conducted.

Results

There were 795,321 ever-users and 619,402 never-users, with respective numbers of incident thyroid cancer of 683 (0.09%) and 1,614 (0.26%), and respective incidence of 24.09 and 87.33 per 100,000 person-years. The overall fully adjusted hazard ratio (95% confidence interval) was 0.683 (0.598–0.780), and all categories of the dose-response parameters showed significantly lower risk with P-trends <0.0001. The protective effect of metformin on thyroid cancer incidence was also supported by sensitivity analyses, disregarding age (<50 or ≥50 years) and sex; and was not affected by excluding users of insulin, sulfonylurea, and insulin and/or sulfonylurea respectively, by previous diagnosis of other cancers or by potential detection examinations that might lead to differential diagnosis of thyroid cancer.

Conclusions

This study provides evidence for the first time that metformin use in patients with type 2 diabetes may reduce the risk of thyroid cancer.     

Tumor Size is an Independent Predictor of Mortality Risk in Differentiated Thyroid Cancer Patients with T4 Disease

Objective: The eighth edition of the American Joint Committee on Cancer (AJCC) guideline on the tumor-node-metastasis staging system has been applied in clinical practice for thyroid cancer since 2018. However, using these criteria, a few studies have shown no significant difference between stage III and IV diseases amongst the differentiated thyroid cancer (DTC) patients. Thus, we aimed to study the underlying reason behind this observation.Methods: Patients were selected from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. The Cox proportional hazards regression model was used for the univariate and multivariate analyses to plot the Kaplan-Meier survival curves for overall survival (OS) and disease-specific survival (DSS).Results: A total of 1,431 patients had a median tumor size of 3.0 cm (range: 0.1 to 50 cm). When stratified by tumor size (≤2 cm, 2 to 4 cm, and >4 cm), lower survival rates were observed in patients with stage III (T4a) cancer and large tumor size than in those with stage IVA (T4b) cancer and small tumor size. Univariate and multivariate analyses showed that tumor size (≤4 cm versus >4 cm) is an independent prognostic factor for OS (P<.001) and DSS (P<.001) in DTC patients with T4a and T4b diseases.Conclusion: Tumor size is an independent prognostic factor for OS and DSS in DTC patients with T4 disease; tumor size-related modification of the T4 category can improve the AJCC staging system for DTC patient with stage III–IV diseases.Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; DSS = disease-specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = Surveillance, Epidemiology, and End Results; TNM = tumor-node-metastasis     

Probabilities of dying from cancer and other causes in French cancer patients based on an unbiased estimator of net survival: A study of five common cancers

BackgroundNet survival is the survival that would be observed if cancer were the only possible cause of death. Although it is an important epidemiological tool allowing temporal or geographical comparisons, it cannot inform on the “crude” probability of death of cancer patients; i.e., when taking into account other possible causes of deaths.MethodsIn this work, we provide estimates of the crude probabilities of death from cancer and from other causes as well as the probability of being alive up to ten years after cancer diagnosis according to the age and year of diagnosis. Based on a flexible excess hazard model providing unbiased estimates of net survival, our methodology avoids the pitfalls associated with the use of the cause of death. We used data from FRANCIM, the French network of cancer registries, and studied five common cancer sites: head and neck, breast, prostate, lung, and colorectal cancers.ResultsFor breast, prostate, and colorectal cancers, the impact of the other causes on the total probability of death increased with the age at diagnosis whereas it remained negligible for lung and head and neck cancers whatever the age. For breast, prostate, and colorectal cancer, the more recently was the cancer diagnosed, the less was the probability of death from cancer.ConclusionThe crude probability of death is an intuitive concept that may prove particularly useful in choosing an appropriate treatment, or refining the indication of a screening strategy by allowing the clinician to estimate the proportion of cancer patients who will die specifically from cancer.     

Programmed Cell Death–Ligand 1 Overexpression in Thyroid Cancer

Objective: Programmed cell death–ligand 1 (PD-L1) expression on tumor tissue has been associated with favorable response to anti–programmed cell death–receptor 1/PD-L1 therapy in many human cancers. Studies have reported that PD-L1 is also expressed in thyroid cancer. The objective of this paper is to introduce the potential predictive and therapeutic values of PD-L1 in thyroid cancer.Methods: A literature search was conducted in the PubMed database using the terms “PD-L1,” “B7-H1,” and “thyroid cancer.” PD-L1 positivity was determined by immunohistochemical assay.Results: The frequency of PD-L1 positivity in different studies ranged from 6.1 to 82.5% in papillary thyroid cancer (PTC) patients and 22.2 to 81.2% in anaplastic thyroid cancer (ATC) patients. PD-L1 positivity rate was higher in ATC than in PTC within the same studies, and its expression intensity was significantly higher in tumor tissue than in the corresponding nontumor thyroid tissues. Moreover, PD-L1 expression was positively associated with the aggressiveness and recurrence of thyroid cancers and negatively associated with the differentiation status and outcomes. PD-L1 checkpoint pathway blockade may emerge as a promising therapeutic target in the treatment of thyroid cancers.Conclusion: PD-L1 is a potential biomarker to predict the recurrence and prognosis of thyroid cancers. It is also a novel immunotherapy target for optimizing the management landscape of radioiodine-refractory and ATCs.Abbreviations: ATC = anaplastic thyroid cancer; DTC = differentiated thyroid cancer; IHC = immunohistochemical; OS = overall survival; PD-1 = programmed cell death–receptor 1; PD-L1 = programmed cell death–ligand 1; PD-L2 = programmed cell death–ligand 2; PTC = papillary thyroid cancer; TNM = tumor-node-metastasis; Treg = regulatory T cell     

Inhibition de ľAccumulation des Chlorophylles dans les Feuilles Primordiales de Phaseolus vulgaris après Irradiation Neutronique

Etiolated bean leaves have been irradiated in an experimental cavity of a nuclear reactor. The greening is allowed either under continuous light or under intermittent light. A relationship between the decrease of the chlorophyll accumulation and the exposure dose is observed; moreover, the accumulation of chlorophyll b is more strongly decreased than the accumulation of chlorophyll a, by irradiation. A recovery phenomenon of the chlorophyll accumulation has been observed. ?auteur remercie le Personnel du Service Exploitation du BR1 et du Département de la Physique des Réacteurs pour le concours précieux apporté, ainsi que Messieurs E. Fagniart, Y. Hauglustaine et Madame El. Bonnijns-Van Gelder pour leur collaboration technique.     

Modelling the Abundances of Two Major Culicoides (Diptera: Ceratopogonidae) Species in the Niayes Area of Senegal

In Senegal, considerable mortality in the equine population and hence major economic losses were caused by the African horse sickness (AHS) epizootic in 2007. Culicoides oxystoma and Culicoides imicola, known or suspected of being vectors of bluetongue and AHS viruses are two predominant species in the vicinity of horses and are present all year-round in Niayes area, Senegal. The aim of this study was to better understand the environmental and climatic drivers of the dynamics of these two species. Culicoides collections were obtained using OVI (Onderstepoort Veterinary Institute) light traps at each of the 5 sites for three nights of consecutive collection per month over one year. Cross Correlation Map analysis was performed to determine the time-lags for which environmental variables and abundance data were the most correlated. C. oxystoma and C. imicola count data were highly variable and overdispersed. Despite modelling large Culicoides counts (over 220,000 Culicoides captured in 354 night-traps), using on-site climate measures, overdispersion persisted in Poisson, negative binomial, Poisson regression mixed-effect with random effect at the site of capture models. The only model able to take into account overdispersion was the Poisson regression mixed-effect model with nested random effects at the site and date of capture levels. According to this model, meteorological variables that contribute to explaining the dynamics of C. oxystoma and C. imicola abundances were: mean temperature and relative humidity of the capture day, mean humidity between 21 and 19 days prior a capture event, density of ruminants, percentage cover of water bodies within a 2 km radius and interaction between temperature and humidity for C. oxystoma; mean rainfall and NDVI of the capture day and percentage cover of water bodies for C. imicola. Other variables such as soil moisture, wind speed, degree days, land cover or landscape metrics could be tested to improve the models. Further work should also assess whether other trapping methods such as host-baited traps help reduce overdispersion.     

Randomization to Screening for Prostate,Lung, Colorectal and Ovarian Cancers and Thyroid Cancer Incidence in Two Large Cancer Screening Trials

Background

Thyroid cancer incidence has increased significantly over the past three decades due, in part, to incidental detection. We examined the association between randomization to screening for lung, prostate, colorectal and/or ovarian cancers and thyroid cancer incidence in two large prospective randomized screening trials.

Methods

We assessed the association between randomization to low-dose helical CT scan versus chest x-ray for lung cancer screening and risk of thyroid cancer in the National Lung Screening Trial (NLST). In the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO), we assessed the association between randomization to regular screening for said cancers versus usual medical care and thyroid cancer risk. Over a median 6 and 11 years of follow-up in NLST and PLCO, respectively, we identified 60 incident and 234 incident thyroid cancer cases. Cox proportional hazards regression was used to calculate the cause specific hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer.

Results

In NLST, randomization to lung CT scan was associated with a non-significant increase in thyroid cancer risk (HR  = 1.61; 95% CI: 0.96–2.71). This association was stronger during the first 3 years of follow-up, during which participants were actively screened (HR  = 2.19; 95% CI: 1.07–4.47), but not subsequently (HR  = 1.08; 95% CI: 0.49–2.37). In PLCO, randomization to cancer screening compared with usual care was associated with a significant decrease in thyroid cancer risk for men (HR  = 0.61; 95% CI: 0.49–0.95) but not women (HR  = 0.91; 95% CI: 0.66–1.26). Similar results were observed when restricting to papillary thyroid cancer in both NLST and PLCO.

Conclusion

Our study suggests that certain medical encounters, such as those using low-dose helical CT scan for lung cancer screening, may increase the detection of incidental thyroid cancer.     

Précisions paléontologiques et stratigraphiques sur divers inocérames cénomaniens et,en particulier,sur ceux de la Sarthe figurés par E. Guéranger en 1867

Modern determinations are given for the Inocerams figured by E. Guéranger in his work «Album paléontologique du département de la Sarthe.The validity of I. angulatus d'Orb. and I. scalprum J. Böhm is discussed as well as the variability of I. virgatusSchlüter.     

Does T Stage Affect Prognosis in Patients With Stage Iv B Differentiated Thyroid Cancer

Objective: Differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, has a relatively good prognosis. The 8^th edition of the American Joint Committee on Cancer (AJCC) pathologic tumor-node-metastasis (T &lsqb;primary tumor size], N &lsqb;regional lymph nodes], M &lsqb;distant metastasis]) staging system did not take the T stage into consideration in stage IV B DTC patients. We evaluated the prognostic value of the T stage for advanced DTC survival.Methods: DTC cases that were considered stage IV B in the AJCC 8^th edition were extracted from the Surveillance, Epidemiology, and End Results database. T stage (AJCC 6^th standard) was categorized into T0–2, T3 and T4. We analyzed overall survival (OS) and cancer specific survival (CSS) in the overall group as well as in pathologic subgroups. We used the Kaplan-Meier method and log-rank test for univariate analysis and the Cox regression model for multivariate analysis.Results: A total of 519 cases were extracted. Patients with earlier T stages showed significantly better OS and CSS in univariate analysis. T stage was an independent prognostic factor for both OS and CSS in multivariate analysis. Subgroup analysis in papillary and follicular thyroid cancer showed that T4 was an independent prognostic factor for both OS and CSS.Conclusion: AJCC 8 stage IV B DTC patients could be further stratified by T stage. Further studies with larger samples and AJCC 8 T stage information are necessary.Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; CSS = cancer specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid carcinoma; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = surveillance, epidemiology, and end results database     

Immunocytochemistry of pectins in shoot apical meristems: consequences for intercellular adhesion

Summary. The nature of pectins (acidic, methyl-, or acetyl-esterified) in the shoot meristem of Sinapis alba was assessed by immunocytochemistry with the 2F4 monoclonal antibody in light and electron microscopy. This antibody is specific for “egg-boxes” – the polygalacturonic acid conformation induced by calcium as described in Liners et al. (Plant Physiol. 99: 1099–1104, 1992). Hardly any acidic pectin was detected in meristem walls; the pectins were largely methyl-esterified and esterified by acetyl groups and/or other esters. After in situ chemical or enzymatic de-esterification, labeling was distributed over the primary wall and the middle lamella of meristematic cells. Acidic pectin and Ca²⁺-cross-linked homogalacturonans were absent from the pit fields, where plasmodesmata traverse the middle lamella. The type and distribution of pectins are discussed in relation to cellular adhesion between active meristem cells. Correspondence and reprints: Unité de Recherches en Biologie Cellulaire Végétale, Département de Biologie, Facultés Universitaires Notre-Dame de la Paix, rue de Bruxelles 61, 5000 Namur, Belgium.     

AZD1480 Blocks Growth and Tumorigenesis of RET- Activated Thyroid Cancer Cell Lines

Persistent RET activation is a frequent event in papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC). In these cancers, RET activates the ERK/MAPK, the PI3K/AKT/mTOR and the JAK/STAT3 pathways. Here, we tested the efficacy of a JAK1/2- inhibitor, AZD1480, in the in vitro and in vivo growth of thyroid cancer cell lines expressing oncogenic RET. Thyroid cancer cell lines harboring RET/PTC1 (TPC-1), RET M918T (MZ-CRC1) and RET C634W (TT) alterations, as well as TPC-1 xenografts, were treated with JAK inhibitor, AZD1480. This inhibitor led to growth inhibition and/or apoptosis of the thyroid cancer cell lines in vitro, as well as to tumor regression of TPC-1 xenografts, where it efficiently blocked STAT3 activation in tumor and stromal cells. This inhibition was associated with decreased proliferation, decreased blood vessel density, coupled with increased necrosis. However, AZD1480 repressed the growth of STAT3- deficient TPC-1 cells in vitro and in vivo, demonstrating that its effects in this cell line were independent of STAT3 in the tumor cells. In all cell lines, the JAK inhibitor reduced phospho-Y1062 RET levels, and mTOR effector phospho-S6, while JAK1/2 downregulation by siRNA did not affect cell growth nor RET and S6 activation. In conclusion, AZD1480 effectively blocks proliferation and tumor growth of activated RET- thyroid cancer cell lines, likely through direct RET inhibition in cancer cells as well as by modulation of the microenvironment (e.g. via JAK/phospho-STAT3 inhibition in endothelial cells). Thus, AZD1480 should be considered as a therapeutic agent for the treatment of RET- activated thyroid cancers.     

Five-year relative survival and determinants of excess mortality in patients with head and neck and thyroid cancers: A population-based study from Golestan province,Northern Iran

BackgroundWe aimed to assess relative survival (RS) and determinants of excess mortality rate in patients with head and neck squamous cell carcinomas (HNSCC) and thyroid cancer in Golestan province, Northern Iran.MethodsWe recruited new primary HNSCC and thyroid cancer cases from Golestan, 2006–2016. Five-year age-standardized RS with their 95% confidence intervals (CIs) were calculated. The relationships between different variables with excess mortality rates were assessed by estimating adjusted excess hazard ratios (aEHRs) with their 95% CIs.ResultsOverall, 718 cases of HNSCC and 386 thyroid cancer cases were enrolled. Five-year age-standardized RS (95% CI) were 36% (31−41) and 61% (52−69) in HNSCC and thyroid cancer patients, respectively. There were significant relationship between excess mortality rates in HNSCC patients with metastasis (aEHR= 3.31; 95%CI: 2.26–4.84), treatment type (4.19; 2.54–6.91, for no treatment as compared to receiving both surgery and chemoradiotherapy), age (2.16; 1.57–2.96, for older age group) and smoking (2.00; 1.45–2.75, for smokers as compared to non-smokers). Determinant of the excess mortality in thyroid cancer patients included metastasis (19.65; 8.08–47.79), tumor morphology (12.27; 4.62–32.58, for anaplastic cancer as compared to papillary cancer), treatment type (8.95, 4.13–19.4, for no treatment as compared to receiving both surgery and iodine therapy) and age (2.31; 1.17–4.54, for older age group).ConclusionOur findings suggested low RS for thyroid cancer in our population, while the estimates for HNSCC were comparable with other population. Metastasis, treatment type and age were determinants of mortality both in thyroid and HNSCC patients.     

An evaluation of the actual incidence of tuberculosis in French Guiana using a capture-recapture model

In order to estimate the level of under-reporting and to improve estimates of the incidence of tuberculosis (TB) in the vicinity of Cayenne, French Guiana, we performed capture-recapture analysis from 1996 through 2003. We cross-linked data from the Institut Pasteur, the Département d'Information Médicale of Cayenne Hospital, and the Service de Lutte Anti-Tuberculeuse. The estimate of 381 TB cases obtained after matching those three sources was revised to 425 (95% confidence interval: 407, 453) using the capture-recapture model based on sample coverage. The corresponding average annual incidence was 63.1 TB cases per 100,000 population. The evaluated sensitivity of the compulsory notification system was 35.3%, indicating wide under-notification of TB in the vicinity of Cayenne. The estimated coverage reported by the three sources was fairly accurate (i.e. 85.9%), but not sufficient to evaluate the risk of transmission of TB in the Ile-de-Cayenne (Cayenne and its suburbs).     

Analysis of thyroid cancer data from the Ukraine after ’Chernobyl’ using a two-mutation carcinogenesis model

The thyroid cancer data of children in the northern regions of the Ukraine after the reactor accident at Chernobyl were combined with thyroid dose measurements in the same regions and analysed using a two- mutation carcinogenesis model. The best fit was obtained for radiation acting as an initiating agent, i.e. on the first mutation of the model. The observed relatively high increase of thyroid cancer incidence after 1990 in children exposed to radiation released after the reactor accident could be ascribed to the high thyroid doses and the relatively low background thyroid cancer incidence in children. The maximum annual incidence is predicted to occur fairly soon after the reactor accident, i.e. about 10 years. For adults, the predicted relative increase of annual thyroid cancers is much lower than for children younger than 20 years. The modelling results are used to derive risk estimates for radiation-induced thyroid cancer. These risk estimates are dependent on age at exposure, follow-up time and the background thyroid cancer incidence. The calculated excess absolute risk for a population of all ages is about one-third of that currently used by ICRP, but for children the calculated absolute risks are about a factor of 3 higher than derived in other epidemiological studies. The model results indicate that the excess absolute radiation risk per unit dose for children is about the same as or a little lower than that for adults. Received: 11 May 1999 / Accepted: 30 December 1999     

Development and Internal Validation of a Predictive Model for Individual Cancer Risk Assessment for Thyroid Nodules

Objective: The objective of this study was to develop and validate a predictive model for the assessment of the individual risk of malignancy of thyroid nodules based on clinical, ultrasound, and analytic variables.Methods: A retrospective case-control study was carried out with 542 patients whose thyroid nodules were analyzed at our endocrinology department between 2013 and 2018 while undergoing treatment for thyroidectomy. Starting with a multivariate logistic regression analysis, which included clinical, analytic, and ultrasound variables, a predictive model for thyroid cancer (TC) risk was devised. This was then subjected to a cross-validation process, using resampling techniques.Results: In the final model, the independent predictors of the risk of malignancy were: being male, age of the extremes, family history of TC, thyroid-stimulating hormone level >4.7 μU/L, presence of autoimmune thyroiditis, solid consistency, hypoechogenicity, irregular or microlobed borders, nodules that are taller than they are wide, microcalcifications, and suspicious adenopathy. With a cut-off point of 50% probability of thyroid cancer, the predictive model had an area under the receiver operating characteristic curve of 0.925 (95% confidence interval 0.898 to 0.952). Finally, using the 10-fold cross-validation method, the accuracy of the model was found to be 88.46%, with a kappa correlation coefficient of 0.62.Conclusion: A predictive model for the individual risk of malignancy of thyroid nodules was developed and validated using clinical, analytic, and ultrasound variables. An online calculator was developed from this model to be used by clinicians to improve decision-making in patients with thyroid nodules.     

Global tyrosine kinome profiling of human thyroid tumors identifies Src as a promising target for invasive cancers

Background: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using a bead-based, high-throughput system.Methods: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room. Protein lysates were analyzed using the Luminex immunosandwich, a bead-based kinase phosphorylation assay. Data was analyzed using GenePattern 3.0 software and clustered according to histology, demographic factors, and tumor status regarding capsular invasion, size, lymphovascular invasion, and extrathyroidal extension. Survival and invasion assays were performed to determine the effect of Src inhibition in papillary thyroid cancer (PTC) cells.Results: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Supervised clustering of well-differentiated tumors by histology, gender, age, or size did not reveal significant differences in tyrosine kinase activity. However, supervised clustering by the presence of invasive disease showed increased Src activity in invasive tumors relative to non-invasive tumors (60% v. 0%, p < 0.05). In vitro, we found that Src inhibition in PTC cells decreased cell invasion and proliferation.Conclusion: Global kinome analysis enables the discovery of novel targets for thyroid cancer therapy. Further investigation of Src targeted therapy for advanced thyroid cancer is warranted.