Thyroid Cancer

Frontiers in Thyroid Cancer: December 2009

Background & Aims: Scientific evidence has shown that there is a correlation between thyroid diseases and cancers and some hematological parameters.This study aimed to determine the relationship between hematological markers and thyroid cancer in patients with thyroid nodules visiting Imam Khomeini Hospital in Urmia. Materials & Methods:In this cross-sectional study, 114 patients diagnosed with thyroid cancer of the FTC (follicular thyroid carcinoma) and PTC (papillary thyroid carcinoma) types and 128 individuals with benign thyroid nodules were included as the control group.Hematological parameters, including hemoglobin level, platelet count, mean platelet volume, lymphocyte count, and neutrophil count, were measured before the initiation of any treatment in the patients.The independent t-test and logistic regression were used to compare the two groups and to establish the relationship between thyroid cancer and hematological parameters.Results: There was no significant difference between the two groups in terms of gender and age (p > 0.05).The average hemoglobin level in patients with thyroid cancer was significantly lower than in the control group (12.85 1.58 vs. 13.51 1.79, p = 0.003), while other parameters did not show a significant difference (p > 0.05).A hemoglobin drop below 12.85 in patients with thyroid cancer was identified as an effective threshold, with the risk of low hemoglobin being 1.28 times higher in patients with thyroid cancer compared to the control group.Other parameters were not identified as significant. Conclusion:A low initial hemoglobin level can be proposed as a preliminary diagnostic parameter for patients with thyroid cancer.The odds ratio of thyroid cancer incidence in patients with Hb less than 12.85 g/dL is 1.28 times higher than in others (p: 0.004).

Aims: To demonstrate the increased risk of developing a second primary thyroid or breast cancer in patients with prior breast or thyroid cancer and to study the clinicopathological characteristic of breast cancer (B2) as a secondary malignancy following a diagnosis of thyroid cancer (T1) or thyroid cancer (T2) following a diagnosis of breast cancer (B1) to find a common aetiology.
 Study Design: Retrospective cohort study
 Place and Duration of Study: Breast & Endocrine Surgery Unit, Surgery Department Hospital Putrajaya between January 2008 and December 2018.
 Methodology: Data of patients with breast cancer as first primary malignancy and thyroid cancers as second primary malignancy, and vice versa, between January 2008 to December 2018 was extracted using electronic search through the hospital information system database and compared for their tumor’s histological type, size, hormonal status (ER/PR), presence of locoregional lymph node and distant metastasis. We also examine any history of radiotherapy for first primary breast cancer patients and history of radioactive iodine ablation for first primary thyroid cancer.
 Results: 1.1% (n:4) of T1 develops B2 while 0.5% (n:8) of B1 develops T2 but we are unable to demonstrate a significant correlation between hormonal status of the tumour, radioiodine ablation or radiation therapy and the risk of developing second primary malignancy.
 Conclusion: There is an increased risk of thyroid cancer as a secondary malignancy following breast cancer and an increased risk of breast cancer as a secondary malignancy following thyroid cancer. No common aetiology can be demonstrated from this study.

BackgroundThyroid diseases are frequent in patients with end-stage renal disease, but data on renal transplant recipients are conflicting. This study evaluated the incidence of thyroid disease and cancer in a population of kidney transplant recipients performed in a single center.MethodsSeven hundred sixty patients receiving a kidney transplantation between January 2000 and October 2017 were followed with thyroid ultrasonography to determine nodules together with thyroid hormone levels. Ultrasound-guided fine-needle aspiration citology (FNAc) was performed to the nodules > 10 mm .ResultsTwo hundred four patients (26.8%) patients demonstrated functional or morphologic changes in the thyroid gland compared with pre-transplant period. Among the 204 patients with newly diagnosed thyroid disease, 165 patients had single or multiple nodular lesions less than 1 cm in diameter, and were followed yearly. Nodule size progression was observed in 23 patients (13.9%), and they underwent a FNAc. A total of sixty-two patients (30.3%) underwent FNAc. The biopsy samples were cytologically interpreted as benign in 20 patients (32.2%), suspicious in 40 patients (64.5%), or at high risk of cancer in 2 patients (3.2%). Forty-two patients underwent total thyroidectomy. At histological examination, 18 patients had a thyroid cancer (papillary cancer in 17 patients, follicular cancer in one). Thyroid cancer was more frequent in male patients with a mean time from transplant to diagnosis of 5.6 years. At a mean follow-up was 8 ± 1.2 years, all patients are alive with a normal functioning graft.ConclusionsThyroid diseases are common in transplant recipients. Thyroid disease may evolve after transplantation, probably as a consequence of immunosuppression. A complete evaluation of thyroid disease is mandatory in kidney transplant recipients because early diagnosis and appropriate treatment of thyroid disease and cancer may significantly decrease the morbidity and mortality in these patients.

Thyroid hyperplasia/multinodular goiter, characterized by cellular and follicular overgrowth, is a very common endocrine condition, resulting in various functional and structural consequences and certain malignant potential. Its genetic background is completely unknown. Given previous genetic and epigenetic data suggesting that RASAL1 might be a thyroid tumor suppressor gene, particularly in follicular thyroid neoplasm, we hypothesized that the RASAL1 gene could play a fundamental role in the development of thyroid hyperplasia/multinodular goiter. To explore the role of the RASAL1 gene in the development of thyroid hyperplasia/multinodular goiter, we developed a novel Rasal1 knockout mouse model using the CRISPR/Cas9 approach and the C57BL/6J zygotes, followed by observing the pathological changes in the thyroid gland of the knockout mice in comparison with the wildtype mice. We successfully created a novel Rasal1 knockout mouse model with establishment of several generations of mice carrying the heterozygous and homozygous knockout of the Ra-sal1 gene at exon 2, which was confirmed by genetic testing and by Western blotting of the Rasal1 protein. All the mice with Rasal1 knockout, whether heterozygous or homozygous, developed grossly visible multinodular goiter with microscopic confirmation of follicular cell hyperplasia, with occasional case showing thyroid cancer. In contrast, only occasional case of aged wild-type mice developed thyroid hyperplasia and no wild-type mice developed thyroid malignancy. These data demonstrate that defect of Rasal1 can cause full and complete development of thyroid hyperplasia/multinodular goiter in mice. Given the striking similarity of thyroid hyperplasia/multinodular goiter in these Rasal1 knockout mice with that in humans, it is plausible to suggest that RASAL1 is a master gene involved in the development and pathogenesis of human thyroid hyperplasia/ multinodular goiter. This project also provides a new genetic knockout mouse model for future study of thyroid neoplasm.

Interpreting I-131 whole-body scans (WBSs) after thyroidectomy for thyroid cancer is not simple. There are scans in which interpretation is speculative because of cryptic findings (CF). Complexity is added in scans that are done a week after an ablative or therapeutic dose of I-131 because not only is I-131-labeled thyroxine (T4) distributed throughout the body, but inorganic I-131 that is derived from the de-iodination of T4 may be also detected. We present our observations regarding the analysis of CF on WBS using I-131 single-photon emission computed tomography (SPECT) in fusion with noncontrast computed tomography (CT), referred to here and elsewhere as I-131 SPECT/CT. Forty of 184 WBSs in 38 thyroidectomized thyroid cancer patients were followed up with I-131 SPECT/CTs. The SPECT/CT images were acquired after a tracer dose of I-131 (n=82) or a week after an ablative or therapeutic dose of I-131 (n=102). Among 184 WBSs, 40 (22%) had CF. In 35 patients the WBS was negative for metastatic disease except for the CF and 5 patients had evidence of thyroid cancer in addition to the CF. There were 49 CF in the planar scans that were localized by SPECT/CT. These were characterized as physiological uptake in gingiva, thymus, gall bladder, menstrual blood, uterine fibroid, recto-sigmoid, colon, and bladder. Also observed was uptake in sites that represented nonthyroidal pathology including dental abscess, hiatal hernia, renal cyst, and struma ovarii. SPECT/CT suggested that 10 of the CF were actually of thyroid origin. In 40 SPECT/CT scans, the images contributed to interpreting the scan. In 15 of 40 patients the SPECT/CT analysis of WBS was performed with tracer doses of I-131 and was important for determining whether to administer ablative I-131 treatment. In another 25 patients, in whom SPECT/CT was performed after ablative or therapeutic doses of 131-I, information regarding the characterization of CF by SPECT/CT was useful in determining if thyroid cancer metastases or thyroid remnants were present. I-131 SPECT/CT is a useful tool to characterize atypical or CF on WBS by differentiating thyroid remnant or cancer from physiologic activity or nonthyroid pathology. In the past, uptake on a WBS that was not explicable as physiologic activity was identified as putative or possible thyroid cancer and generally was treated with I-131. Now, by identifying activity in some possible cancer sites as not thyroid cancer, SPECT/CT can reduce inappropriate treatment with I-131. SPECT/CT of WBS performed after ablative doses of 131-I is useful in determining the nature of CF and therefore likely providing prognostic information.

To the editor, The incidence of pediatric thyroid cancer has increased worldwide, and the age-standardized incidence rate in South Korea was 0.92 per 100,000 person-years during 2004-2016, with an annual percentage of 4.0% [1].Pediatric patients, comprised mostly of those with papillary thyroid cancer (PTC, 80%-90%), typically present with a palpable neck mass with advanced stage, and the recurrence rate is high.However, cancer-specific mortality is low, showing a good long-term survival prognosis.Oncogenic fusions (RET, NTRK, ALK, etc.) predominated in children younger than 10 years with PTC, whereas point mutations (BRAF, etc.) increased with age, becoming most common in adolescents aged 15-19 years [2].Pediatric follicular thyroid carcinoma (FTC) has a very low frequency (<10%), with a more favorable prognosis than PTC.DICER1 and PTEN mutations predominate in pediatric FTC [3], and the possibility of hereditary tumor syndrome needs to be excluded.Considering the differential biologic features of pediatric thyroid cancer compared to adult thyroid cancer, pediatric-specific guidelines are needed.We, the Korean Thyroid Association (KTA) Guideline Committee on the Managements of Thyroid Nodule and Cancer, published the guideline for pediatric differentiated thyroid cancer (DTC) in International Journal of Thyroidology in May 2024 [4].The 2024 KTA pediatric DTC guideline consists of 7 parts: preoperative evaluation, children at high risk for developing DTC, surgery, initial treatment and follow-up strategy, radioactive iodine (RAI) therapy, recurrent or persistent disease, and RAI-refractory thyroid cancer (Supplementary Table 1).Below are the essential aspects of the KTA pediatric guideline [4]:

Breast cancer (BC) and thyroid cancer (TC) have the highest rate of incidence, especially in women. Previous studies have revealed that lactate provides energetic and anabolic support to cancer cells, thus serving as an important oncometabolite with both extracellular and intracellular signaling functions. However, the correlation of lactate metabolism scores with thyroid and breast cancer immune characteristics remains to be systematically analyzed. To investigate the role of lactate at the transcriptome level and its correlation with the clinical outcome of BC and TC, transcriptome data of 1,217 patients with breast cancer (BC) and 568 patients with thyroid cancer (TC) were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets with their corresponding clinical and somatic mutation data. The lactate metabolism score was calculated based on a single-sample gene set enrichment analysis (ssGSEA). The results showed that lactate metabolism-related genes and lactate metabolism scores was significantly associated with the survival of patients with BRCA and THCA. Notably, the lactate metabolism scores were strongly correlated with human leukocyte antigen (HLA) expression, tumor-infiltrating lymphocyte (TIL) infiltration, and interferon (IFN) response in BC and TC. Furthermore, the lactate metabolism score was an independent prognostic factor and could serve as a reliable predictor of overall survival, clinical characteristics, and immune cell infiltration, with the potential to be applied in immunotherapy or precise chemotherapy of BC and TC.

Mapping overdiagnosis of thyroid cancer in China

A new study points to disparities in thyroid cancer incidence between specific age and ethnic groups, but the authors and others say that its findings tell only part of the story and that more research needs to be performed.The study, presented in Orlando, Florida, at ENDO 2017, the annual scientific meeting of the Endocrine Society, shows that the incidence of thyroid cancer is rising among young people and among Hispanics and African Americans.Although the incidence of the disease appears to be increasing at a slower rate now than it was a few years ago, that slowing has occurred mainly among non-Hispanic whites and older populations, whereas the rate of thyroid cancer has continuously increased in young and Hispanic and black populations according to Anupam Kotwal, MBBS, a clinical fellow in the Division of Endocrinology, Diabetes, Metabolism, and Nutrition at the Mayo Clinic in Rochester, Minnesota.Kotwal has been working with Mayo Clinic endocrinologist Juan Brito Campana, MBBS, to examine how sex, racial, and age disparities play a role in the diagnosis of thyroid cancer, access to care, and its management.The study may have implications for disease-specific outcomes as well as societal and economic costs, he notes."[Thyroid cancer] is the most common cancer in Hispanic females, female adolescents, and young adults.

It has been shown that the etiology of thyroid, breast and prostate cancer is associated with hereditary and some environmental factors that cause damage to DNA. Protein coding genes are responsible for the development of protein and thus have been reported to be good candidate susceptibility genes for thyroid, breast and prostate cancer. (FOSL1) proteins have important functions in the growth, including the regulation of cell proliferation, differentiation and transformation. There have been studies of elevated levels of FOSL1 in cancers. However, the available methods for measuring FOSL1 levels are direct and quantitative using Poly Chain Reaction (RT-PCR) in real time. In the present study, whole blood was isolated from 100 individuals distributed into four groups as follows: Group 1 included: 25 samples from thyroid cancer patients; Group 2: 25 samples from breast cancer patients; Group 3: 25 samples from prostate cancer and Group 4:25 samples from apparently healthy individuals. The messenger RNA (mRNA) expression levels of FOSL_1in the peripheral blood was analyzed using reverse transcription polymerase chain reaction (RT PCR). The expression of FOSL_1 mRNA in the fold of gene expression in prostatic cancer group was 4 time higher than that of healthy group. That for the breast cancer group was 3 times higher than the healthy group and the thyroid cancer group was 3 times higher than the healthy group., respectively, Using GAPDH as Housekeeping Gene. In conclusion, there is an important link between blood and tumor tissue expression of FOSL1 gene. in thyroid, breast and prostate cancer, could allow the introduction in clinical practice of a simple test that would measure mRNA levels of DNA protein coding genes in peripheral blood samples instead of tissue samples; thus justifying its use as a prognostic and predictive factors in thyroid, breast and prostate cancer patients.

Increased Incidence of Melanoma, Prostate, Lung, Bladder, Renal and Thyroid Cancer after Diagnosis of Primary Cutaneous B-Cell Lymphoma: A SEER Database Analysis

The sharply increasing incidence of thyroid cancer has attracted considerable attention over the last few years. The combination of surgery, radioiodine ablation and thyroid-stimulating hormone suppression is usually efficient for the majority of thyroid tumors. However, advanced thyroid cancer that is recurrent, metastatic and 131I-refractory, or medullary thyroid cancer, pose a therapeutic challenge. Autophagy is a process that metabolizes damaged cytoplasmic organelles and long-lived proteins in order to recycle cellular materials and maintain homeostasis. It has been confirmed that autophagy plays a dual role during cancer development, progression and treatment, mainly depending on the type and stage of the tumor. Autophagy modulation has become a potential therapeutic target for diverse diseases. The mechanism of thyroid tumorigenesis and cancer progression was largely demonstrated to be correlated with the dysregulation of the Ras/Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase and the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathways, as well as with abnormal epigenetic modifications. Those mechanisms are associated with autophagy regulation and may be beneficial for the treatment of advanced thyroid cancer. However, the number of available studies on the role of autophagy in thyroid cancer development, progression and treatment outcome, is currently limited. The aim of this review was to elaborate on the relevant knowledge and future prospectives of autophagy in the treatment of thyroid cancer.

With increasing numbers of childhood cancer survivors who were treated with radiation, there is a need to evaluate potential biomarkers that could signal an increased risk of developing thyroid cancer. We aimed to examine the relationships between thyrotropin and thyroglobulin levels and the risk of developing thyroid nodules and cancer in a cohort of radiation-exposed children. 764 subjects who were irradiated in the neck area as children were examined and followed for up to 25 years. All subjects underwent a clinical examination, measurements of thyrotropin, thyroglobulin levels and thyroid imaging. At baseline, 216 subjects had thyroid nodules and 548 did not. Of those with nodules, 176 underwent surgery with 55 confirmed thyroid cancers. During the follow-up, 147 subjects developed thyroid nodules including 22 with thyroid cancer. Thyroglobulin levels were higher in subjects with prevalent thyroid nodules (26.1 ng/mL vs 9.37 ng/mL; P < 0.001) and in those who had an initial normal examination but later developed thyroid nodules (11.2 ng/mL vs 8.87 ng/mL; P = 0.017). There was no relationship between baseline thyrotropin levels and the prevalent presence or absence of thyroid nodules, whether a prevalent neoplasm was benign or malignant, subsequent development of thyroid nodules during follow-up or whether an incident nodule was benign or malignant. In conclusion, in radiation-exposed children, higher thyroglobulin levels indicated an increased risk of developing thyroid nodules but did not differentiate between benign and malignant neoplasms. There was no association between the baseline TSH level and the risk of developing thyroid nodules or cancer.

<title>Abstract</title> Objective(s): 1. The common differential genes of breast cancer and thyroid cancer were identified by Gene Express Omnibus database (GEO). The Cancer Genome Atlas (TCGA) database was used to determine the relationship between the screened differential genes and the clinicopathologic features. Gene set enrichment analysis (GSEA) was used to identify the enrichment pathways of the differential genes in breast and thyroid cancers.2. Retrospective studies were conducted to analyze the relationship between the general characteristics, clinicopathological features, and hormone expression levels in patients with dual cancers of breast cancer combined with thyroid cancer and patients with breast cancer and thyroid cancer alone, and to further analyze the KRT19 expression levels in their tissues. analyze the expression of KRT19 protein in their tissues. Method(s): 1. Download the datasets GSE70947 and GSE3467 from the GEO database, analyze the differential genes of breast cancer, thyroid cancer and normal tissues respectively by using R, and take the intersection of the differential genes of the two tissues to continue the next step of the study. 2. Download the mRNA-seq data of the above differential genes of BRCA and THCA from the TCGA database, and identify the differences in expression of differential genes between normal tissues and tumor tissues by using the above differential gene substitution in R. Gene set enrichment analysis (GSEA) identifies the differences in expression of differential genes enriched in breast and thyroid cancer. Differential gene substitution analysis, and identify the differences in differential gene expression between normal and tumor tissues, Gene set enrichment analysis (GSEA) to identify the pathways of enrichment in breast and thyroid cancers, and then screened out the representative differential gene KRT19 (human cytokeratin 19).3. Collect the mRNA-seq data of BRCA and THCA in the database of TCGA, and use the R language in the substitution analysis of the above differential genes, and identify the differences in differential gene expression between normal and tumor tissues. 3. July 2023 in Zhongshan People's Hospital and puncture or surgical treatment of breast cancer combined with thyroid cancer patient data, a total of 92 cases (experimental group), another randomly collected in the past two years in Zhongshan People's Hospital in the simple breast cancer patients 100 cases (control group 1), thyroid cancer patients, 100 cases (control group 2). 4. the experimental group and the control group 1, 2 of the patient pathology data for Pathological data of patients in experimental and control groups 1 and 2 were retrospectively analyzed, and additional surgical bulk or puncture specimens were subjected to immunohistochemical staining (IHC) to examine the expression of KRT19 protein in the tissues, and to explore whether there was a difference in its expression between experimental and control groups. Result(s): 1. KRT19 mRNA levels were significantly overexpressed in breast and thyroid cancer tissues as analyzed by the GEO database, and KRT19 was associated with clinicopathological features of breast and thyroid cancers as analyzed by the TCGA database, and the GSEA showed that both the breast and thyroid cancer-KRT19 overexpression groups were significantly enriched in the estrogen-responsive pathway.2. In the dual-primary cancer group, of which breast cancer preceded In the dual-primary cancer group, breast cancer preceded thyroid cancer in 86 cases and thyroid cancer preceded in 6 cases, i.e., breast cancer preceded thyroid cancer in the vast majority of patients (&gt; 90%). Compared with the breast cancer group, the dual-primary cancer group was younger at the time of diagnosis, more often in the premenopausal state, with a larger tumor size, and more often positively expressed estrogen receptors (ER) and progesterone receptors (PR), with a statistically significant difference (all <italic>P</italic> &lt; 0.050). Compared with the thyroid cancer group, the odds of tumors occurring bilaterally were increased in the double primary cancer group, and the levels of triiodothyronine (T3) and thyroxine (T4) (both <italic>P</italic> &lt; 0.050) were significantly higher. KRT19 was more frequently positively expressed in breast cancer than in breast cancer alone in dual primary cancers ( <italic>P</italic> = 0.069), and in thyroid cancer than in thyroid cancer alone in dual primary cancers ( <italic>P</italic> &lt; 0.050). Conclusion(s): Pathogenesis correlates between breast and thyroid cancers, estrogen receptor expression is associated with dual carcinogenesis, and KRT19 influences dual carcinogenesis through the estrogen response pathway.