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JAMA Network Open Aug 2023To our knowledge, there are no complete population-based studies of the risks of developing second malignant tumors after papillary thyroid carcinoma (PTC) in patients...
IMPORTANCE
To our knowledge, there are no complete population-based studies of the risks of developing second malignant tumors after papillary thyroid carcinoma (PTC) in patients following the Chernobyl nuclear accident.
OBJECTIVE
To study the risk of second primary cancers in patients with PTC after the Chernobyl disaster.
DESIGN, SETTING, AND PARTICIPANTS
This was a retrospective cohort study conducted in the Republic of Belarus over a 31-year time frame evaluating patients with primary PTC and second malignant tumors. Personal data from the Belarussian Cancer Registry were used in the investigation, and only second primary cancers were included in the analysis. Patients were observed from January 1, 1990, to December 31, 2021, for the establishment of second primary malignant tumors.
MAIN OUTCOMES AND MEASURES
For analysis, synchronous and metachronous tumors were grouped into 1 group (second primary cancer group). If the patient had more than 2 cancers, they were observed until development of a second tumor and, subsequently, the development of a third tumor. The starting point for calculating the number of person-years was the date of thyroid cancer diagnosis. The end point for calculating the number of person-years was the date of diagnosis of the second primary malignant tumor, the date of death, the date of the last visit of the patient, or December 31, 2021 (the end the of study period). The incidence of a second primary malignant tumor with PTC was calculated for the study groups using standardized incidence ratios.
RESULTS
Of the 30 568 patients with a primary PTC included in this study, 2820 (9.2%) developed a second malignant tumor (2204 women and 616 men); the mean (SD) age of all patients at time of the primary cancer was 53.9 (12.6) years and at time of the secondary cancer was 61.5 (11.8) years. Overall, the standardized incidence ratio was statistically significant for all types of cancer (1.25; 95% CI, 1.21-1.30), including solid malignant tumors (1.20; 95% CI, 1.15-1.25) and all leukemias (1.61; 95% CI, 2.17-2.13). Cancers of the digestive system (466 cases [21.1%]), genital organs (376 cases [17.1%]), and breasts (603 cases [27.4%]) were the most prevalent second primary tumors in women following PTC. Second primary tumors of the gastrointestinal tract (146 cases [27.7%]), genitourinary system (139 cases [22.6%]), and urinary tract (139 cases [22.6%]) were the most prevalent in men. Urinary tract cancers (307 cases [10.9%]) and gastrointestinal tumors (612 cases [21.4%]) were the most prevalent second primary tumors overall.
CONCLUSIONS AND RELEVANCE
This cohort study reports the increased incidence of solid secondary tumors in men and women over a 31-year time frame after the Chernobyl disaster. Moreover, there was a statistically significant increased risk of second tumors of the breast, colon, rectum, mesothelium, eye, adnexa, meninges, and adrenal glands as well as Kaposi sarcoma. These data might have an effect on the follow-up of this cohort of patients to detect secondary malignant tumors at an early stage.
Topics: Male; Humans; Female; Middle Aged; Neoplasms, Second Primary; Thyroid Cancer, Papillary; Chernobyl Nuclear Accident; Cohort Studies; Retrospective Studies; Thyroid Neoplasms; Disasters
PubMed: 37589974
DOI: 10.1001/jamanetworkopen.2023.29559 -
Frontiers in Endocrinology 2023The management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However,...
BACKGROUND
The management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However, in distinct types DTC, differences in RAI avidity and response existed and the effect of RAI therapy could not be equated.
METHODS
DTC patients' data in SEER database were extracted to perform retrospective analysis. The differences between case group and control group were compared by chi-square tests. We used Kaplan-Meier statistics and Cox regression analyses to investigate cancer-specific survival (CSS). Propensity score-matched was performed to make 1:1 case-control matching.
RESULTS
105195 patients who receiving total thyroidectomy were identified in SEER database. Compared to papillary thyroid carcinoma (PTC) (52.3%), follicular thyroid carcinoma (FTC) (63.8%) and oncocytic carcinoma of thyroid (OCA) (64.4%) had higher rates of RAI therapy. In the multivariable Cox regression model, RAI therapy was independent prognosis factor in PTC but not in OCA and FTC. In subgroup analysis, RAI therapy could improve prognosis in PTC when gross extrathyroidal extension or lymph node metastases or early survival when distant metastases (DM) were presented. However, OCA and FTC patients with DM rather than regional lesions only could benefit from RAI therapy. High-risk patients receiving RAI therapy showed a better prognosis in PTC but not in OCA and FTC.
CONCLUSION
RAI therapy was an effective treatment for DTC and should be considered individually in PTC, OCA and FTC patients. Our results provided further guideline for treatment selection in DTC.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Propensity Score; Retrospective Studies; Adenocarcinoma, Follicular; Thyroid Cancer, Papillary
PubMed: 37664843
DOI: 10.3389/fendo.2023.1158581 -
Frontiers in Oncology 2023Diagnosis and treatment of multiple primary malignancies are becoming a new challenge in clinical practice worldwide. The present study aimed to characterize the...
Diagnosis and treatment of multiple primary malignancies are becoming a new challenge in clinical practice worldwide. The present study aimed to characterize the clinical and genetic features of multiple primary malignancies in patients with synchronous or metachronous lymphoma and another solid tumor. We retrospectively analyzed 11 cases with lymphoma and another solid tumor. The germline mutations in plasma cell-free DNA samples and somatic mutations in lymphoma and solid tumor tissue samples were identified using targeted next-generation sequencing. In the 11 lymphoma patients, the most common type of concurrent solid tumor was colon adenocarcinoma (case 3, 5, 9 11) followed by papillary thyroid carcinoma (case 1, 7, 10). Metachronous lymphoma and solid tumor in 6 patients were treated with corresponding standard therapy asynchronously. Chemotherapy for colon adenocarcinoma during the interval of lymphoma chemotherapy led to excellent outcome in two patients. Immediate chemotherapy for lymphoma plus elective surgery for synchronous papillary thyroid carcinoma also yielded good prognosis in two patients with synchronous double primaries. Interestingly, we found that 10 of 11 patients with lymphoma and another solid tumor harbored germline mutations in Fanconi anemia complementation group (FANC) genes, including FANCI, FANCA, FANCG, FANCL, FANCD1, FANCF, FANCJ, and FANCS. In summary, comprehensive study of the clinical and genetic features of patients with multiple primary malignancies may improve diagnosis and treatment in the future. Mutations in FANC genes might be a predisposition to tumorigenesis of lymphoma patients with a second solid malignancy.
PubMed: 37546421
DOI: 10.3389/fonc.2023.1152290 -
Frontiers in Endocrinology 2023Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). Several genomic and transcriptomic studies explored the molecular landscape of...
BACKGROUND
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). Several genomic and transcriptomic studies explored the molecular landscape of follicular cell-derived TCs, and V600E, mutations, and gene fusions are well-established drivers. mutations were described in specific sets of TC patients but represent a rare event in adult TC patients.
METHODS
Here, we report the molecular characterization of 30 retrospective follicular cell-derived thyroid tumors, comprising PTCs (90%) and poorly differentiated TCs (10%), collected at our Institute. We performed DNA whole-exome sequencing using patient-matched control for somatic mutation calling, and targeted RNA-seq for gene fusion detection. Transcriptional profiles established in the same cohort by microarray were investigated using three signaling-related gene signatures derived from The Cancer Genome Atlas (TCGA).
RESULTS
The occurrence of V600E (44%), mutations (13%), and gene fusions (13%) was confirmed in our cohort. In addition, in two patients lacking known drivers, mutations of the gene (p.D1709N and p.D1810V) were identified. mutations occur in two adult patients with follicular-pattern lesions, and in one of them a second concurrent mutation (p.R459*) is also observed. Additional putative drivers include gene (p.P2130A mutation), identified in a patient with a rare solid-trabecular subtype of PTC. Transcriptomics indicates that tumors are RAS-like, whereas the -mutated tumor displays a borderline RAS-/BRAF-like subtype. We also provide an overview of and mutations in thyroid lesions by investigating the COSMIC database.
CONCLUSION
Even though small, our series recapitulates the genetic background of PTC. Furthermore, we identified mutations, one of which is previously unreported in thyroid lesions. For these less common alterations and for patients with unknown drivers, we provide signaling information applying TCGA-derived classification.
Topics: Humans; Adult; Transcriptome; Retrospective Studies; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Thyroid Neoplasms; Thyroid Cancer, Papillary; Mutation; Genomics; Ribonuclease III; DEAD-box RNA Helicases
PubMed: 37867524
DOI: 10.3389/fendo.2023.1267499 -
Aging Jul 2023Non-SMC condensin I complex subunit D2 (NCAPD2) is overexpressed in some malignant tumors. However, there are few studies on the function of NCAPD2 in pan-cancer. We...
Non-SMC condensin I complex subunit D2 (NCAPD2) is overexpressed in some malignant tumors. However, there are few studies on the function of NCAPD2 in pan-cancer. We used the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), and UALCAN to analyze NCAPD2 expression and promoter methylation levels in 33 tumors and normal samples. We performed immunohistochemistry (IHC) on liver cancer and corresponding normal tissues to examine NCAPD2 protein expression in LIHC. Kaplan-Meier survival and univariate regression analyses were performed to explore the pan-cancer clinical significance of NCAPD2. Moreover, correlative analysis between NCAPD2 expression and clinical characteristics, immune cell infiltration, immune checkpoints, immune regulators, tumor mutation burden (TMB), microsatellite instability (MSI), ribonucleic acid (RNA) methylation regulators, and drug sensitivity was conducted using data from TCGA. We also investigated the effects of NCAPD2 expression on immunotherapy efficacy and prognosis. Gene set enrichment analysis (GSEA) was conducted using NCAPD2. Bioinformatic analysis showed that NCAPD2 was overexpressed in most tumors and correlated with the clinical characteristics of some cancers. IHC results demonstrated that NCAPD2 protein expression was higher in LIHC than in normal liver. NCAPD2 expression was linked with T stage, clinical stage, and histologic grade in LIHC. Overexpression of NCAPD2 resulted in poor overall survival, and disease-specific survival in adrenocortical carcinoma, kidney renal papillary cell carcinoma, brain lower grade glioma, liver hepatocellular carcinoma, lung adenocarcinoma, mesothelioma, pancreatic adenocarcinoma, sarcoma, skin cutaneous melanoma, and uterine corpus endometrial carcinoma. NCAPD2 was considered an independent biomarker by Cox regression in LIHC. The time ROC curve demonstrated that the survival rate of 1-, 3-, and 5-year OS and DSS in LIHC was above 0.6. The expression of NCAPD2 was significantly correlated with immune cell infiltration, immune checkpoints, TMB, MSI, and RNA methylation regulators in several tumors. NCAPD2 had a high predictive value for immunotherapy efficiency in certain tumors. In our study, drugs sensitive to NCAPD2 protein were screened by sensitivity analysis. GSEA analysis showed that NCAPD2 mainly participated in the G2M checkpoint, mitotic spindle, and KRAS-signaling. NCAPD2 may act as a prognostic molecular marker in most cancers.
Topics: Humans; Melanoma; Prognosis; Adenocarcinoma; Skin Neoplasms; Pancreatic Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Kidney Neoplasms; Lung Neoplasms; Adrenal Cortex Neoplasms; Poly-ADP-Ribose Binding Proteins; Chromosomal Proteins, Non-Histone; Melanoma, Cutaneous Malignant
PubMed: 37498296
DOI: 10.18632/aging.204904 -
Scientific Reports Aug 2023The most common BRAF mutation is thymine (T) to adenine (A) missense mutation in nucleotide 1796 (T1796A, V600E). The BRAF gene encodes a protein-dependent kinase (PDK),... (Randomized Controlled Trial)
Randomized Controlled Trial
The most common BRAF mutation is thymine (T) to adenine (A) missense mutation in nucleotide 1796 (T1796A, V600E). The BRAF gene encodes a protein-dependent kinase (PDK), which is a key component of the mitogen-activated protein kinase pathway and essential for controlling cell proliferation, differentiation, and death. The BRAF mutation causes PDK to be activated improperly and continuously, resulting in abnormal proliferation and differentiation in PTC. Based on elastography ultrasound (US) radiomic features, this study seeks to create and validate six distinct machine learning algorithms to predict BRAF mutation in PTC patients prior to surgery. This study employed routine US strain elastography image data from 138 PTC patients. The patients were separated into two groups: those who did not have the BRAF mutation (n = 75) and those who did have the mutation (n = 63). The patients were randomly assigned to one of two data sets: training (70%), or validation (30%). From strain elastography US images, a total of 479 radiomic features were retrieved. Pearson's Correlation Coefficient (PCC) and Recursive Feature Elimination (RFE) with stratified tenfold cross-validation were used to decrease the features. Based on selected radiomic features, six machine learning algorithms including support vector machine with the linear kernel (SVM_L), support vector machine with radial basis function kernel (SVM_RBF), logistic regression (LR), Naïve Bayes (NB), K-nearest neighbors (KNN), and linear discriminant analysis (LDA) were compared to predict the possibility of BRAF. The accuracy (ACC), the area under the curve (AUC), sensitivity (SEN), specificity (SPEC), positive predictive value (PPV), negative predictive value (NPV), decision curve analysis (DCA), and calibration curves of the machine learning algorithms were used to evaluate their performance. ① The machine learning algorithms' diagnostic performance depended on 27 radiomic features. ② AUCs for NB, KNN, LDA, LR, SVM_L, and SVM_RBF were 0.80 (95% confidence interval [CI]: 0.65-0.91), 0.87 (95% CI 0.73-0.95), 0.91(95% CI 0.79-0.98), 0.92 (95% CI 0.80-0.98), 0.93 (95% CI 0.80-0.98), and 0.98 (95% CI 0.88-1.00), respectively. ③ There was a significant difference in echogenicity,vertical and horizontal diameter ratios, and elasticity between PTC patients with BRAF and PTC patients without BRAF. Machine learning algorithms based on US elastography radiomic features are capable of predicting the likelihood of BRAF in PTC patients, which can assist physicians in identifying the risk of BRAF in PTC patients. Among the six machine learning algorithms, the support vector machine with radial basis function (SVM_RBF) achieved the best ACC (0.93), AUC (0.98), SEN (0.95), SPEC (0.90), PPV (0.91), and NPV (0.95).
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Elasticity Imaging Techniques; Proto-Oncogene Proteins B-raf; Bayes Theorem; Carcinoma, Papillary; Mutation; Machine Learning
PubMed: 37537230
DOI: 10.1038/s41598-023-39747-6 -
International Journal of Molecular... Nov 2023Thyroid cancer is the predominant endocrine-related malignancy. ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) has been studied in various types of cancers;...
Thyroid cancer is the predominant endocrine-related malignancy. ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) has been studied in various types of cancers; however, the expression and function of ST6GAL1 in thyroid cancer has not been investigated so far. Previously, we conducted two genome-wide association studies and have identified the association of the gene with plasma thyroglobulin (Tg) levels. Since Tg levels are altered in thyroid pathologies, in the current study, we wanted to evaluate the expression of ST6GAL1 in thyroid cancer tissues. We performed an immunohistochemical analysis using human thyroid tissue from 89 patients and analyzed ST6GAL1 protein expression in papillary thyroid cancer (including follicular variant and microcarcinoma) and follicular thyroid cancer in comparison to normal thyroid tissue. Additionally, mRNA levels from The Cancer Genome Atlas (TCGA, n = 572) and the Genotype-Tissue Expression (GTEx) project (n = 279) were examined. The immunohistochemical analysis revealed higher ST6GAL1 protein expression in all thyroid tumors compared to normal thyroid tissue. TCGA data revealed increased mRNA levels in both primary and metastatic tumors versus controls. Notably, the follicular variant of papillary thyroid cancer exhibited significantly higher mRNA levels than classic papillary thyroid cancer. High mRNA levels significantly correlated with lymph node metastasis status, clinical stage, and reduced survival rate. ST6GAL1 emerges as a potential cancer-associated glycosyltransferase in thyroid malignancies, offering valuable insights into its diagnostic and prognostic significance.
Topics: Humans; Thyroid Cancer, Papillary; Genome-Wide Association Study; Thyroid Neoplasms; Genomics; RNA, Messenger; beta-D-Galactoside alpha 2-6-Sialyltransferase; Antigens, CD
PubMed: 38003522
DOI: 10.3390/ijms242216334 -
Frontiers in Endocrinology 2023Subclinical hypothyroidism is the most common thyroid dysfunction. Approximately 10% of patients with thyroid cancer have subclinical hypothyroidism. There is a paucity...
BACKGROUND
Subclinical hypothyroidism is the most common thyroid dysfunction. Approximately 10% of patients with thyroid cancer have subclinical hypothyroidism. There is a paucity of real-world studies examining the relationship between subclinical hypothyroidism and known correlates of invasiveness of papillary thyroid carcinoma (PTC).
MATERIALS AND METHODS
A retrospective cohort study of 13,717 patients with PTC was conducted. Odds ratios were calculated to assess the relationship between subclinical hypothyroidism and extrathyroidal extension (ETE) after adjusting for BMI and genders. The Cancer Genome Atlas (TCGA) data were utilized for the analysis of TSHR-associated pathways, while qRT-PCR was employed to validate the expression levels of pivotal genes in the relevant signaling pathways.
RESULTS
In total, 13,717 PTC patients (10,769 women and 2,948 men; mean [SD] age, 42.90 [9.43] years) were included in the retrospective study. Subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.168 [95% CI, 1.028-1.327]; =0.017). In normal-weight patients, subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.287 [95% CI, 1.089-1.520]; =0.003). However, this risk was not observed in under-weight, overweight, and obese patients. Compared to females, subclinical hypothyroidism was a higher risk factor for ETE in male patients with normal body weight (OR male=2.363 vs. OR female=1.228). Subclinical hypothyroidism was found to be a significant risk factor for ETE in the subgroup of patients younger than 38 years old (OR1 adjusted, 1.382 [95% CI, 1.032-1.852], =0.030). The findings from Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed the involvement of the autophagy signaling pathway in TSHR/ETE/EMT regulation. Moreover, the gene expression levels demonstrated a concentration-dependent relationship between TSH intervention levels and the expression of key genes in the autophagy pathway of thyroid cancer cells.
CONCLUSION
Subclinical hypothyroidism was an independent risk factor for ETE in patients with PTC. This association was particularly significant in normal-weight and younger patients. The risk of ETE associated with subclinical hypothyroidism was higher in males compared to females. Our study indicates a potential involvement of the autophagy pathway in regulating the ETE phenotype in thyroid cancer, specifically in the context of subclinical hypothyroidism.
Topics: Humans; Male; Female; Adult; Thyroid Cancer, Papillary; Retrospective Studies; Carcinoma, Papillary; Thyroidectomy; Thyroid Neoplasms; Hypothyroidism
PubMed: 38174330
DOI: 10.3389/fendo.2023.1294441 -
The International Journal of Biological... Dec 2023Papillary thyroid carcinoma is the most common malignancy of the endocrine system. Most papillary thyroid carcinoma patients enjoy excellent outcomes. However, in...
The clinical and pathological significance of increased expression of the cannabinoid receptors CB-1R and CB-2R in patients with papillary thyroid carcinomas compared to benign thyroid lesions.
INTRODUCTION
Papillary thyroid carcinoma is the most common malignancy of the endocrine system. Most papillary thyroid carcinoma patients enjoy excellent outcomes. However, in patients with biologically aggressive features, additional prognostic and predictive data may aid disease management. Dysregulation of the endocannabinoid system including the cannabinoid receptors 1 and 2 (CB-1R and CB-2R) during carcinogenesis has been extensively studied over the last few decades. The aim of this study was to evaluate immunohistochemically the expression levels of both receptors in patients with papillary thyroid carcinoma and benign diseases, and to compare these rates and the histopathologically and clinically prognostic features.
METHODS
The pathological materials and clinical data of 100 patients with papillary thyroid carcinoma and 40 with benign diseases were retrospectively re-evaluated. All tissues were immunohistochemically stained for CB-1R and CB-2R. The expression levels of CB-1R and CB-2R in papillary thyroid carcinomas, and benign lesions were recorded and compared with the pathological and clinical features.
RESULTS
The expression levels of both receptors were significantly higher in papillary thyroid carcinoma patients than in those with benign conditions (= 0.001). CB-1R expression correlated with both extrathyroidal extension (= 0.022) and capsular invasion (= 0.001). CB-2R expression was associated with the risk group of the American Thyroid Association stratification system (= 0.004).
CONCLUSION
Our study suggests that increased cannabinoid receptor expression contributes to thyroid carcinogenesis. The CB-2R expression level could provide additional information aiding risk management. Furthermore, the CB-1R and CB-2R antibodies might increase the accuracy of papillary thyroid carcinoma diagnosis when combined with the papillary thyroid carcinoma biomarkers assayed after fine-needle aspiration of neoplastic cells.
Topics: Humans; Carcinogenesis; Carcinoma, Papillary; Retrospective Studies; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 37700679
DOI: 10.1177/03936155231200285 -
Oncology (Williston Park, N.Y.) May 2024Well-differentiated papillary mesothelioma (WDPM) is a rare mesothelial tumor of uncertain malignant potential. We present a unique case of a woman with synchronous WDPM...
Well-differentiated papillary mesothelioma (WDPM) is a rare mesothelial tumor of uncertain malignant potential. We present a unique case of a woman with synchronous WDPM and well-differentiated endometrioid adenocarcinoma (EA) arising from extraovarian endometriosis. A 56-year-old postmenopausal woman presented with a several-month history of right lower quadrant abdominal pain. She had a history of supracervical hysterectomy and bilateral salpingo-oophorectomy secondary to endometriosis. Imaging reported a mass in the right lower quadrant originating from the distal ileum. At laparotomy, the patient underwent a right colectomy with resection of the terminal ileum and excision of a solitary peritoneal nodule. Pathology was consistent with a diagnosis of well-differentiated EA (arising from extraovarian endometriosis) and WDPM. Further treatment consisted of complete surgical staging/debulking and adjuvant chemotherapy directed toward metastatic well-differentiated EA. Surgeons should be familiar with WDPM as a potential finding in women of reproductive age undergoing abdominal surgery for any indication.
Topics: Humans; Female; Middle Aged; Endometriosis; Carcinoma, Endometrioid; Mesothelioma; Neoplasms, Multiple Primary; Endometrial Neoplasms
PubMed: 38776516
DOI: 10.46883/2024.25921020