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Impact of Hashimotoas thyroiditis on clinicopathologic features of papillary thyroid carcinoma associated with infiltration of tumor-infiltrating lymphocytes.

ABSTRACT: The association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) has been a long and ongoing controversy. In the present study, a total number of 322 patients who underwent thyroidectomies were retrospectively studied, and the impact of HT with the incidence, clinicopathologic features, and presence of CD4+, CD8+ tumor-infiltrating lymphocytes (TILs) in PTC patients were analyzed. We further explored the correlation between CD4+, CD8+ TILs and clinicopathologic features in PTC patients with and without HT. The incidence of HT concurrent with PTC was 42.9%, which was significantly associated with a younger age (P=0.039) and the presence of hyperthyroid (P=0.010). The PTC patients coexistent with HT tended to be more female (P=0.001), with diffuse swelling of the thyroid (P<0.001), decreased TSH (P=0.004), and elevated anti-TgAb (P<0.001) and anti-TPOAb (P<0.001). The tumor size of PTC with HT was smaller (P=0.006) and exhibited more bilateral tumors (P<0.001) and less lymph node metastasis (P=0.016). Furthermore, CD4+ and CD8+ TILs in PTC with HT were significantly higher than without HT (both P<0.001). Both high CD4+ and CD8+ TILs were significantly associated with elevated TSH (P=0.019 and P=0.023, respectively), anti-TgAb (P=0.002 and P=0.001, respectively) and anti-TPOAb (P=0.001 and P=0.003, respectively), and the tumor size was smaller (P=0.017 and P=0.039, respectively) and with less lymph node metastasis (P=0.012 and P<0.001, respectively) in PTC with HT. Our study suggests that HT is significantly associated with PTC, which might be ascribed to infiltration of CD4+, CD8+ TILs.

SUBMITTER: Wang L

PROVIDER: S-EPMC6958247 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Impact of Hashimotoas thyroiditis on clinicopathologic features of papillary thyroid carcinoma associated with infiltration of tumor-infiltrating lymphocytes.

Wang Lin L Li Weiwei W Ye Hong H Niu Li L

International journal of clinical and experimental pathology 20180501 5

The association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) has been a long and ongoing controversy. In the present study, a total number of 322 patients who underwent thyroidectomies were retrospectively studied, and the impact of HT with the incidence, clinicopathologic features, and presence of CD4+, CD8+ tumor-infiltrating lymphocytes (TILs) in PTC patients were analyzed. We further explored the correlation between CD4+, CD8+ TILs and clinicopathologic features ...[more]

PMID: 31938394

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Project description:Hashimoto's thyroiditis (HT) is present in the background of around 30% of papillary thyroid carcinomas (PTCs). The genetic predisposition effect of this autoimmune condition is not thoroughly understood. We analyzed the microarray expression profiles of 13 HT, eight PTCs with (w/) coexisting HT, six PTCs without (w/o) coexisting HT, six micro PTCs (mPTCs), and three normal thyroid (TN) samples. Based on a false discovery rate (FDR)-adjusted p-value ? 0.05 and a fold change (FC) > 2, four comparison groups were defined, which were HT vs. TN; PTC w/ HT vs. TN; PTC w/o HT vs. TN; and mPTC vs. TN. A Venn diagram displayed 15 different intersecting and non-intersecting differentially expressed gene (DEG) sets, of which a set of 71 DEGs, shared between the two comparison groups HT vs. TN ? PTC w/ HT vs. TN, harbored the relatively largest number of genes related to immune and inflammatory functions; oxidative stress and reactive oxygen species (ROS); DNA damage and DNA repair; cell cycle; and apoptosis. The majority of the 71 DEGs were upregulated and the most upregulated DEGs included a number of immunoglobulin kappa variable genes, and other immune-related genes, e.g., CD86 molecule (CD86), interleukin 2 receptor gamma (IL2RG), and interferon, alpha-inducible protein 6 (IFI6). Upregulated genes preferentially associated with other gene ontologies (GO) were, e.g., STAT1, MMP9, TOP2A, and BRCA2. Biofunctional analysis revealed pathways related to immunogenic functions. Further data analysis focused on the set of non-intersecting 358 DEGs derived from the comparison group of HT vs. TN, and on the set of 950 DEGs from the intersection of all four comparison groups. In conclusion, this study indicates that, besides immune/inflammation-related genes, also genes associated with oxidative stress, ROS, DNA damage, DNA repair, cell cycle, and apoptosis are comparably more deregulated in a data set shared between HT and PTC w/ HT. These findings are compatible with the conception of a genetic sequence where chronic inflammatory response is accompanied by deregulation of genes and biofunctions associated with oncogenic transformation. The generated data set may serve as a source for identifying candidate genes and biomarkers that are practical for clinical application.

Project description:BackgroundHashimoto's thyroiditis (HT) is the most prevalent inflammatory disorder of the thyroid gland. Current studies have reported the coexistence rate between HT and papillary thyroid carcinoma (PTC) is quite high. The objective of this study was to evaluate the impact of HT on the predictive factors of central compartment lymph node metastasis (CLNM) in PTC.MethodsA retrospective investigation was performed on PTC patients. They were subclassified into HT and non-HT groups. The results of preoperative neck ultrasound (US) examinations were reviewed. The clinical characteristics and the predictive value for CLNM were explored and compared between the two groups.ResultsA total of 756 patients were included in this study. There were more female patients (86.1%) in the PTC coexistent with the HT group than non-HT group. The patients with HT group had higher preoperative serum level of TSH. There was statistically significant difference between the HT patients and non-HT patients in nodular vascularization. Univariate and multivariate analyses showed that male, age ≤45 years old, tumor diameter >1 cm, and presence of suspicious central compartment lymph node on US, irregular nodular shape, multifocal carcinoma were independent predictive factors of CLNM in PTC patients. It was showed that male, age ≤45 years old, tumor diameter >1 cm, multifocality, and presence of suspicious central lymph node on US were risk factors for CLNM in non-HT patients. Only tumor diameter >1 cm and presence of suspicious central lymph node on US were independently correlated with CLNM in HT patients. The sensitivity of the multivariate model was 63.5%, and specificity was 88.9% for prediction CLNM in HT patients. For non-HT patients, the AUC was 80.6%, the sensitivity of the multivariate model was 64.5%, and specificity was 85.2.ConclusionPTC combined with HT is more common in women, and TSH level in HT group is higher than that in patients with PTC alone. Regardless of that HT is not a related risk factor of CLNM in PTC, our result suggested that different predictive systems should be used for HT and non-HT patients respectively to have a more accurate evaluation of CLNM in clinic.

Project description:The aim of the present study was to evaluate the association between coexisting lymphocytic thyroiditis (LT) and the clinicopathological features of papillary thyroid carcinoma (PTC). The records of 458 patients with PTC who underwent a total thyroidectomy and lymph node dissection in Sir Run Run Shaw Hospital (Hangzhou, China) were analyzed. In accordance with the histopathology of thyroid parenchyma, the cases were divided into three groups, including Hashimoto's thyroiditis (HT), non-Hashimoto's type LT (NHLT) and no LT. Based on the histopathology, data on age, sex, maximum diameter of tumor, multifocality, extrathyroidal extension, metastatic lymph node size, extranodal extension and tumor grades in the different groups were analyzed and compared. The prevalence of coexisting LT was 29.0% (133/458), of which 7.6% (35/458) was HT and 21.4% (98/458) was NHLT. PTC concomitant with LT was significantly associated with female patients (95.5 vs. 70.2%; P<0.001), a lower rate of extrathyroidal extension and/or capsular invasion (25.6 vs. 39.7%; P=0.004), central lymph node metastasis (CLNM) ratio (10.71 vs. 17.37; P=0.014), higher number of dissected central lymph nodes (16.83 vs. 11.7; P<0.001), larger metastatic lymph nodes (0.66 vs. 0.46 cm; P<0.001), higher occurrence of multifocality (61.7 vs. 50.5%; P=0.029) and earlier pT stage (57.9 vs. 38.8%; P<0.001), regardless of the combined or separate consideration of HT and NHLT. Besides, LT was associated with multifocality [odds ratio (OR), 1.578; 95% confidence interval (CI), 1.046-2.382; P=0.030]. Furthermore, in patients with PTC, CLNM had a significant association with the male sex (OR, 2.000; 95% CI, 1.216-3.288; P=0.006), an age of <45 years (OR, 0.592; 95% CI, 0.398-0.879; P=0.009) and a tumor size of >1 cm (OR, 3.913; 95% CI, 2.431-5.734; P<0.001). In conclusion, patients with PTC and LT showed a greater female preponderance, multifocality, a lower extrathyroidal extension and a lower CLNM ratio. LT was associated with an increased risk of multifocality in PTC.

Project description:BackgroundThe association between adiposity and papillary thyroid carcinoma (PTC) has been reported in several studies, but its association with aggressive clinicopathologic features is not well-recognized. Our aim is to systematically review the literature to identify whether adiposity, expressed through Body Mass Index (BMI), is related to aggressive clinicopathologic features such as tumor-node-metastasis (TNM) stage, extrathyroidal extension (ETE), lymph node (LN) metastasis and multifocality in patients with PTC.MethodsA systematic search for articles was performed using the PubMed, EBSCO, and Cochrane Library for all articles published in English until December 2020. Specific keywords such as "papillary thyroid carcinoma", "Body Mass Index", "clinicopathologic features" were used in the search strategy. Two independent reviewers screened all retrieved articles based on predefined inclusion and exclusion criteria. Meta-analysis was performed in the studies that reported crude and adjusted odds ratios (OR). The methodological quality was assessed using the Newcastle-Ottawa Scale.ResultsA total of 11 retrospective cohort studies involving 26,196 participants included. Our findings showed that elevated BMI was significantly associated with ETE in both overweight (OR 1.26, 95% CI: 1.09-1.44) and obesity group (OR 1.45, 95% CI:1.26-1.64). Elevated BMI was also significantly associated with multifocality in overweight patients (OR 1.17, 95% CI:1.10-1.24) and obese patients (OR 1.45, 95% CI:1.29-1.62). Also, obesity was significantly associated with increased tumor size (OR 1.77, 95% CI:1.52-2.03) and with LN metastasis (OR 1.28, 95% CI: 1.12-1.44), whereas being overweight was significantly associated with advanced TNM stage (OR 1.55, 95% CI:1.27-1.83).ConclusionOur results provide strong evidence for the association between higher BMI and ETE, multifocality, and tumor size. Further studies with a larger number of participants are required to elucidate further the association of increased BMI with advanced TNM stage and LN metastasis.

Dataset Information

Impact of Hashimotoas thyroiditis on clinicopathologic features of papillary thyroid carcinoma associated with infiltration of tumor-infiltrating lymphocytes.

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Impact of Hashimotoas thyroiditis on clinicopathologic features of papillary thyroid carcinoma associated with infiltration of tumor-infiltrating lymphocytes.

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