Project description:Pulmonary metastases from thyroid carcinoma typically cause a micronodular or miliary pattern throughout both lungs. Metastasis consisting of a solitary pulmonary nodule measuring 20 mm in diameter is rare. Here we report a case of a 66-year-old woman without a history of papillary thyroid carcinoma who presented with a pulmonary nodule measuring 20 mm in diameter, found on chest computed tomography during a health checkup. The patient underwent a right lobectomy. Microscopic examination showed well-differentiated papillary adenocarcinoma. Immunohistochemical findings were consistent with a diagnosis of pulmonary metastasis from papillary thyroid carcinoma. Solitary metastasis to the lung from occult thyroid carcinoma is quite rare, but if a pulmonary nodule is encountered in a patient without a history of thyroid carcinoma, the possibility must be considered.
Project description:Background/objectivesA modern classification distinguishes between two nosological entities posing an intermediate risk between differentiated and anaplastic carcinoma: poorly differentiated thyroid carcinoma and differentiated high-grade thyroid carcinoma. There are currently few studies searching for the preoperative molecular genetic markers of high-grade papillary thyroid carcinoma (PTC HG), primarily because of a recent WHO reclassification and singling out of a separate entity: high-grade follicular cell-derived nonanaplastic thyroid carcinoma. Therefore, this work was aimed at identifying PTC HG-specific microRNAs and mRNAs that reliably distinguish them from differentiated papillary thyroid carcinoma in preoperative cytology specimens (fine-needle aspiration biopsies).MethodsA molecular genetic profile (expression levels of 14 genes and eight microRNAs) was studied in 110 cytology specimens from patients with PTC: 13 PTCs HG and 97 PTCs without features of HG.ResultsOf the examined eight microRNAs and 14 genes, significant differences in the expression levels between the PTC and PTC HG groups were revealed for genes SLC26A7, TFF3, and TPO. Only one gene (SLC26A7) proved to be crucial for detecting PTC HG. It showed the largest area under the ROC curve (0.816) in differentiation between the PTC and PTC HG groups and was the key element of the decision tree by ensuring 54% sensitivity and 87.6% specificity.ConclusionsEarly preoperative diagnosis of PTC HG in patients with early stages of this cancer type will allow clinicians to modify a treatment strategy toward a larger surgery volume and lymph node dissection and may provide indications for subsequent radioactive iodine therapy.
Project description:BackgroundThe objective of this study is to develop a predictive model for the assessment of cervical lymph node metastasis risk in papillary thyroid carcinoma (PTC).MethodsA retrospective study was conducted on 212 patients with PTC who underwent initial surgical treatment from August 2022 to April 2023 in 2 hospitals. Data were randomly split into 7:3 training-validation sets. Logistic regression was used for feature selection and predictive model creation. Model performance was assessed using receiver operating characteristic (ROC) and calibration curves. Clinical utility was determined using decision curves.ResultsAmong the 212 patients with PTC, 104 cases (49.1%) exhibited cervical lymph node metastasis, while 108 cases (50.9%) did not. Multivariate logistic regression analysis revealed that age (OR = 0.95), FT3 (OR = 0.41), tumor maximum diameter ≥0.9 cm (OR = 1.85), intratumoral microcalcifications (OR = 1.84), and suspicious lymph node on ultrasound (OR = 2.96) were independent risk factors for lymph node metastasis in PTC patients (P < 0.05). The constructed model for predicting the risk of cervical lymph node metastasis demonstrated a training set ROC curve area under the curve (AUC) of 0.742 (95% CI: 0.664 - 0.821), with a cut-off value of 0.615, specificity of 87.8%, and sensitivity of 51.4%. The validation set exhibited an AUC of 0.648 (95% CI: 0.501 - 0.788), with a cut-off value of 0.644, specificity of 91.2%, and sensitivity of 43.3%. Including the BRAF V600 E mutation did not improve the model's diagnostic performance significantly. Decision curve analysis indicated clinical feasibility of the model.ConclusionThe predictive model developed in this study effectively predicts lymph node metastasis risk in PTC patients by incorporating ultrasound features, demographic characteristics, and serum parameters. However, including the BRAF V600 E mutation does not significantly improve the model's diagnostic performance.
Project description:Lin28 is involved in the progression of several types of tumors. Data collected from clinical trials have suggested that Lin28 expression is correlated with poor prognosis in thyroid carcinoma. The present study was conducted to investigate the association between Lin28 expression and the clinicopathological parameters of papillary thyroid carcinoma (PTC). Accordingly, the clinical data and diagnostic results from 237 patients with PTC were collected. Immunohistochemical staining was performed to evaluate the Lin28 expression levels in thyroid tissue samples. Associations between the expression levels and clinicopathological parameters were evaluated. Lin28 was expressed in 96/237 (40.5%) of PTC specimens. Compared with patients with no Lin28 expression, patients with expression had higher rates of lymph node metastasis (P<0.001) and larger tumors (P=0.011). Multivariate analysis revealed that Lin28 was associated with lymph node metastasis. Next, bioinformatics analysis was performed based using the Gene Expression Omnibus database and The Cancer Genome Atlas database. Lin28 expression was associated with aggressive tumor characteristics, such as lymph node metastasis and larger tumors. In conclusion, the present study revealed that Lin28 expression served as a risk factor for lymph node metastasis. Accordingly, Lin28 expression may be used as a prognostic marker to predict lymph node metastasis in patients with PTC. In addition, Lin28 may serve as a therapeutic target in the management of this tumor type, which may help improve patient outcomes.
Project description:We performed oligonucleotide microarray analysis to assess the genetic expression alteration wich affected on lateral neck node metastasis of thyroid papillary microcarcinoma(PTMC). We performed microarray analysis in three PTMCs without cervical lymph-node metastases (N0), and five PTMCs with lateral neck-node metastasis (N1b) at initial diagnosis, using an Illumina HumanHT-12 v4.0 Expression BeadChip.
Project description:BackgroundPapillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland, with lymph node metastasis significantly affecting patient prognosis. In recent years, body mass index (BMI) has garnered widespread attention as a potential factor influencing cancer development. This study aimed to explore the relationship between BMI and lymph node metastasis in patients with PTC, particularly focusing on the risk of metastasis in the lateral and central neck compartments.MethodsThis retrospective study comprised 993 patients who underwent surgical treatment and were pathologically confirmed to have PTC. Patient BMI data were collected, and their relationship with lymph node metastasis in the lateral and central neck compartments was analyzed. Logistic regression models were employed to analyze the correlation between BMI and lymph node metastasis.ResultsThe study found a significant correlation between BMI and the risk of lateral neck lymph node metastasis in patients (P=0.008), along with a corresponding increase in extrathyroidal extension risk (P=0.02). While elevated BMI did not directly increase the risk of central compartment metastasis, a significant increase was observed in the number of central compartment lymph node metastases (P=0.009) and their proportion among the total central compartment lymph nodes (P=0.01) in patients with higher BMI. Additionally, multifocality, age, and gender were identified as risk factors for lateral neck lymph node metastasis, whereas Hashimoto's thyroiditis did not exhibit a similar impact.ConclusionsThis study highlights that higher BMI is an important risk factor for lateral neck lymph node metastasis in patients with PTC and may exacerbate the severity of central compartment lymph node metastasis. These findings underscore the importance of considering BMI in the management of thyroid cancer and provide data support for future prevention and intervention strategies.
Project description:BackgroundThyroid cancer is prevalent worldwide, including in China, where its incidence is on the rise. Papillary thyroid carcinoma (PTC) is the predominant subtype. Investigating the relationship between clinical data associated with PTC and gene mutations is crucial for improving detection and treatment.Patients and methodsWe collected samples and associated clinical data from 700 PTC patients at Shanxi Provincial People's Hospital. Using a panel of 57 genes linked to thyroid cancer, we sequenced the samples to determine the mutation frequency of thyroid cancer-associated genes in PTC. We further analyzed the correlation between gene variants and clinical information.ResultsThe mean age of patients in this study was 42.5 years. Females predominated, comprising 507 of the total patient population, resulting in a female-to-male ratio of 2.63 (507:193). Tumor distribution revealed 198, 257, and 142 cases on the left, right, and both sides, respectively. Among the 57 thyroid cancer-related genes analyzed, we identified at least one driver gene in 83.6% of patients. Notably, 76.4% had BRAF mutations, mainly BRAFV600E, which constituted 90.9% of all BRAF mutations, with 535 cases exhibiting these mutations. Other significant driver genes included CHEK2 (n = 84), RET (n = 42), PIK3CA (n = 7), and EGFR (n = 7). RET fusions (n = 28) were also identified. Notably, patients under 55 years old exhibit a higher tendency towards advanced N staging, suggesting that younger individuals may be more prone to lymph node metastasis. Additionally, male patients were more likely to have advanced N stages. Importantly, a positive correlation was observed between higher BRAF allele frequencies and more advanced T and N stages. Similarly, correlation analysis revealed that a greater frequency of RET fusions correlated with later T and N stages.ConclusionThis study uncovered several significant insights. Younger PTC patients exhibited a higher propensity for lymph node metastasis. An elevated mutation frequency of BRAF was correlated with a higher occurrence of RET fusions, predisposing individuals to lymph node metastasis and potentially indicating a poorer prognosis.
Project description:BackgroundDistant metastasis (DM) is a rare event and has a negative effect on the prognosis for papillary thyroid carcinoma (PTC). The relationship between cervical lymph node metastasis and DM is complicated and unclear. This study aimed to evaluate the impact of N stage subclassification on different distant metastasis sites based on age stratification, especially for patients with papillary thyroid microcarcinoma.MethodsA total of 28,712 patient with PTC cases between 2010 and 2018 were extracted from the Surveillance, Epidemiology, and End Results database. Multivariable logistic regression analysis was utilized to adjust for confounding variables. Risk stratification, including positive lymph node number and lymph node ratio, was established by receiver operating characteristic curves to help predict DM.ResultsLung was the most common metastatic site regardless of N0, N1a disease, or N1b disease. As the N stage increased, the higher the rate of DM identified. After age stratification, only N1b disease significantly increased the risk of lung metastasis (LM; odds ratio, OR = 20.45, P < 0.001) rather than bone metastasis (BM; OR = 3.46, P > 0.05) in younger patients. However, in older patients, N1b disease significantly increased the risk of both LM (OR = 4.10, P < 0.001) and BM (OR = 2.65, P = 0.007). In patients with papillary thyroid microcarcinoma (PTMC), N1a disease did not increase the risk of DM, LM, and BM compared with N0 disease (P > 0.05). Furthermore, combined N stage with risk stratification has well performance in predicting DM (area under the curve, AUC = 0.761). Similar results were shown in PTC patients with LM (AUC = 0.770) and BM (AUC = 0.729).ConclusionOverall, the incidence of DM significantly increased with the progress of N disease after age stratification. N1a disease did not increase the risk of DM in PTMC patients, regardless of LM or BM. Combined N stage with risk stratification may be beneficial for DM prediction.
Project description:BackgroundPrevious studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear.MethodsWe compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC.ResultsOur results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration.ConclusionsOur study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis.
Project description:A high prevalence of thyroid papillary cancer was reported in hepatitis-C-virus (HCV) positive patients. However, the mechanistic role of hepatic-fibrosis in thyroid malignancy progressions is still unclear.We aimed to study the immune-modulatory interactions between thyroid papillary carcinoma and hepatic-fibrosis.Hepatic-fibrosis was induced in nude-nu-male mice by intra-peritoneal administration of carbon-tetrachloride. To induce thyroid-tumor, a thyroid papillary carcinoma cell line (NPA) was injected subcutaneously in the backs. Fibrotic profile was estimated by α-smooth-muscle-actin (αSMA) expression in liver tissue extracts using western-blots and RT-PCR. Intra-hepatic NK cells were isolated and stained for NK activity (CD107a) by flow cytometry. Liver histopathology (H&E staining), thyroid tumor mass and serum alanine aminotransferase (ALT), serum vascular endothelial growth factor (VEGF) and free-T4 levels were also assessed.Ex-vivo: NPA cells were co-cultured with intra-hepatic NK cells isolated from fibrotic mice with/without the tumor were analyzed for CFSE-proliferations. Both tumor groups (with/without hepatic-fibrosis) excreted higher serum free T4 levels. Hepatic-fibrosis increased tumor weight and size and serum free-T4 levels. In addition, tumor induction increased liver injury (both hepatic-fibrosis, necro-inflammation and serum ALT levels). In addition, tumor-bearing animals with hepatic-fibrosis had increased NK activity. NPA tumor-bearing animals increased fibrosis in spite of increased NK activity; probably due to a direct effect through increased serum free-T4 excretions. Serum VEGF levels were significantly increased in the fibrotic- bearing tumor groups compared to the non-fibrotic groups. In-vitro, NK cells from fibrotic tumor-bearing animals reduced proliferation of NPA cells. This decrease is attributed to increase NK cells activity in the fibrotic animals with the NPA tumors.Our results propose that NK cells although were stimulated in advanced fibrosis with tumor, they lost their anti-tumor and anti-fibrotic activity probably due to secretions of T4 and VEFG and may explain increased risk of thyroid tumors in chronic HCV patients.