Implications of isthmic location as a risk factor in papillary thyroid carcinoma
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SUBMITTER: Kwon O
PROVIDER: S-EPMC10506121 | biostudies-literature | 2023 Jul
REPOSITORIES: biostudies-literature
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Project description:PurposeTreatment protocols for occult central lymph node metastasis (LNM) associated with papillary thyroid cancer (PTC) located in the isthmus are debatable. We aimed to analyze the pattern of occult central LNM in isthmic PTC, including risk factors for bilateral paratracheal LNM.Patients and MethodsConsecutive patients with PTC were recruited to this study. All patients underwent total thyroidectomy and prophylactic bilateral central neck dissection. The clinicopathologic features and distribution of central LNM were compared between the two groups, and risk factors for bilateral paratracheal LNM were analyzed.ResultsA total of 174 patients with PTC were enrolled in this study, of whom 87 patients had isthmic PTC (study group) and 87 patients had lobe-originating PTC (control group). The two groups had comparable demographics and tumor features. There were higher frequencies of pretracheal LNM (P =0.001) and bilateral paratracheal LNM (P = 0.002) in the isthmic PTC group. Bilateral paratracheal LNM was significantly associated with age <55 years (P = 0.037), capsular invasion (P = 0.034), tumor location (isthmus) (P < 0.001), BRAF gene mutation (P = 0.013), and pretracheal LNM (P < 0.001). Isthmus location (odds ratio [OR]: 4.116, 95% confidence interval [CI]: 1.264–13.433, P = 0.019) and pretracheal LNM (OR: 3.422, 95% CI: 1.214–9.642, P = 0.020) were independent risk factors for bilateral paratracheal LNM.ConclusionBecause of its unique anatomic location, isthmic PTC differs from PTC in the lobe with respect to pretracheal and bilateral paratracheal LNM, even in patients of comparable age, sex, tumor size, extrathyroidal extension, BRAF mutation, and pathologic TNM staging. The isthmus location was found to be an independent risk factor for bilateral paratracheal LNM. This information may contribute to the development of an appropriate surgical protocol for isthmic PTC.
| S-EPMC7245435 | biostudies-literature
Project description:BackgroundAlthough most papillary thyroid carcinoma (PTC) cases have a good prognosis, some PTCs are more aggressive and are often accompanied by lymph node (LN) metastasis, a high recurrence rate, and poor prognosis. Distinguishing highly invasive metastatic PTC is an urgent problem that needs to be addressed clinically. We analyzed a microarray of metastasized PTC and validated it using quantitative reverse transcription PCR (RT-qPCR) and immunohistochemistry to identify biomarkers that can be used to assess the risk of PTC metastasis.MethodsThe microarray of metastasized PTC was screened using the Gene Expression Omnibus (GEO) database. The differences between cancer and normal tissues were analyzed using the official GEO tool: GEO2R. Gene expression profile data (GEPIA) were used to verify the expression of differential genes in large samples and to analyze their correlation. The Kaplan-Meier plotter (KM-plotter) database was used for the analysis of genes potentially related to survival. RT-qPCR was used to check the expression of risk factor genes in pathological sections from PTC patients with clinical LN metastasis. Immunohistochemistry was used to verify the expression of core risk-associated genes.ResultsFourteen PTC metastasis-associated genes were identified. In metastasized PTC, CLDN1, LRP4, LRRK2, and TENM1 were highly expressed, whereas DIO1, DPP6, HGD, IPCEF1, MT1F, SLC26A4, SLC26A7, SPX, TFF3, and TPO were expressed at low levels, compared to expression in normal tissues. DIO1, HGD, SLC26A4, and TPO were found to be the core risk genes in the PTC metastatic risk set. Results based on clinical samples showed that the expression differences for metastasis risk-associated genes were consistent with the bioinformatics analysis results.ConclusionsFourteen differentially expressed genes (CLDN1, LRP4, LRRK2, TENM1, DIO1, DPP6, HGD, IPCEF1, MT1F, SLC26A4, SLC26A7, SPX, TFF3, TPO) are associated with an increased risk of PTC metastasis, and DIO1, HGD, SLC26A4, and TPO are the key risk-associated genes in this set that might affect the occurrence and development of PTC through iodine metabolism. These genes could provide a reference for clinical metastatic PTC risk evaluation and treatment.
| S-EPMC9714616 | biostudies-literature
Project description:BackgroundThyroid carcinoma is a common pediatric head and neck cancer, of which papillary thyroid cancer (PTC) is the most common type. Previously, we found that thyroid peroxidase (TPO) and aldehyde oxidase 1 (AOX1) were differentially expressed in PTC. This study explored the clinical importance of TPO and AOX1 in the diagnosis and prognosis of PTC in children.MethodsBoth TPO and AOX1 expression in PTC were analyzed using datasets from Gene Expression Omnibus (GEO). TPO and AOX1 protein levels in plasma from patients with PTC and non-tumor controls were detected via enzyme-linked immunosorbent assay (ELISA). The diagnostic accuracy of TPO and AOX1 was assessed using receiver operating characteristic (ROC) curve analysis. The association between gene expression levels and patient survival was explored using the Kaplan-Meier plotter online database.ResultsThe results revealed that TPO and AOX1 expression was significantly downregulated in four independent datasets (GSE33630, GSE27155, GSE3678, and GSE3467). TPO and AOX1 protein levels in blood plasma were significantly decreased in patients with PTC. Quantitative analysis demonstrated that TPO and AOX1 levels in plasma had satisfactory predictive performance and the ability to discriminate PTC from healthy samples. Prognostic analysis demonstrated that low levels of TPO and AOX1 were markedly associated with poor survival in patients with PTC.ConclusionsIn summary, these results implied that TPO and AOX1 could serve as novel biomarkers for the diagnosis and prognosis of pediatric PTC.
| S-EPMC8107839 | biostudies-literature
Project description:The strong genetic predisposition to papillary thyroid carcinoma (PTC) might be due to a combination of low-penetrance susceptibility variants. Thus, the research into gene variants involved in the increase of susceptibility to PTC is a relevant field of investigation. The gene coding for the receptor-type tyrosine phosphatase PTPRJ has been proposed as a cancer susceptibility gene, and its role as a tumor suppressor gene is well established in thyroid carcinogenesis. In this study, we want to ascertain the role of PTPRJ genotype in the risk for PTC. We performed a case-control study in which we determined the PTPRJ genotype for the non-synonymous Gln276Pro and Asp872Glu polymorphisms by PCR amplification and sequencing. We calculated allele and genotype frequencies for the considered polymorphisms of PTPRJ in a total sample of 299 cases (PTC patients) and 339 controls (healthy subjects) selected from Caucasian populations. We observed a significantly higher frequency of homozygotes for the Asp872 allele in the group of PTC patients than in the control group (odds ratio=1.61, 95% confidence interval 1.15-2.25, P=0.0053). We observed a non-significant increased frequency of homozygotes for Gln276Pro polymorphism in PTC cases in two distinct Caucasian populations. Therefore, the results reported here show that the homozygous genotype for Asp872 of PTPRJ is associated with an increased risk to develop PTC.
| S-EPMC3915780 | biostudies-literature
Project description:Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies. The most common etiologic factor is radiation, but genetic susceptibility and other factors also contribute to the development of papillary thyroid carcinoma. The most common variants include conventional, follicular variant and tall cell variant. However, many other uncommon variants have been described including oncocytic, columnar cell, diffuse sclerosing and solid forms. Immunohistochemical staining with TTF-1 and thyroglobulin is very useful in confirming the diagnosis of papillary thyroid carcinoma especially in metastatic sites. Markers such as HBME-1 and CITED1 can assist in separating some difficult cases of follicular variants of papillary thyroid carcinomas from follicular adenomas. Molecular studies have shown that the BRAF V600E mutation is found mainly in papillary and anaplastic thyroid carcinomas. Other molecular markers such as HMGA2 and insulin-like growth factor II mRNA binding protein 3 have been used recently as molecular tests to separate papillary thyroid carcinoma and its variants from follicular adenomas and other benign thyroid nodules.
| S-EPMC3037461 | biostudies-literature
Project description:BackgroundAs a rare but aggressive papillary thyroid carcinoma (PTC) variant, the genetic changes of hobnail variant of PTC (HVPTC) are still unclear.ResultsThe prevalence of HVPTC was 1.69% (18/1062) of all PTC diagnosed in our cohort. 73 samples from 55 patients (17 HVPTC, 26 CPTC, 7 PDTC and 5 ATC) were successfully analyzed using targeted NGS with an 18-gene panel. Thirty-seven mutation variant types were identified among 11 genes. BRAF V600E mutation was the most common mutation, which is present in almost all HVPTC samples (16/17, 94%), most CPTC samples (20/26, 77%), and none of the ATC and PDTC samples. TERT promoter mutation (C228T) was identified in 2 ATC and one HVPTC patient. RAS and TP53 mutation are almost exclusively present among ATC and PDTC samples although TP53 mutation was also observed in 3 HVPTC patients. Six different GNAS mutations were identified among 8 CPTC patients (31%) and none of the HVPTC patients. The only patient who died of disease progression harbored concomitant TERT C228T mutation, BRAF V600E mutation and TP53 mutation.MethodsHVPTC cases were identified from a group of 1062 consecutive surgical specimens diagnosed as PTC between 2000 and 2010. Targeted next-generation sequencing (NGS) was applied to investigate the mutation spectrum of HVPTC, compared to classical PTC (CPTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC).ConclusionAs an aggressive variant of PTC, HVPTC has relatively specific molecular features, which is somewhat different from both CPTC and ATC/PDTC and may underlie its relatively aggressive behavior.
| S-EPMC5400643 | biostudies-literature
Project description:Thyroid nodules (TNs) represent a common scenario. More accurate pre-operative diagnosis of malignancy has become an overriding concern. This study incorporated demographic, serological, ultrasound, and biopsy data and aimed to compare a new diagnostic prediction model based on Back Propagation Neural Network (BPNN) with multivariate logistic regression model, to guide the decision of surgery. Records of 2,090 patients with TNs who underwent thyroid surgery were retrospectively reviewed. Multivariate logistic regression analysis indicated that Bethesda category (OR=1.90, P<0.001), TIRADS (OR=2.55, P<0.001), age (OR=0.97, P=0.002), nodule size (OR=0.53, P<0.001), and serum levels of Tg (OR=0.994, P=0.004) and HDL-C (OR=0.23, P=0.001) were statistically significant independent differentiators for patients with PTC and benign nodules. Both BPNN and regression models showed good accuracy in differentiating PTC from benign nodules (area under the curve [AUC], 0.948 and 0.924, respectively). Notably, the BPNN model showed a higher specificity (88.3% vs. 73.9%) and negative predictive value (83.7% vs. 45.8%) than the regression model, while the sensitivity (93.1% vs. 93.9%) was similar between two models. Stratified analysis based on Bethesda indeterminate cytology categories showed similar findings. Therefore, BPNN and regression models based on a combination of demographic, serological, ultrasound, and biopsy data, all of which were readily available in routine clinical practice, might help guide the decision of surgery for TNs.
| S-EPMC9483149 | biostudies-literature
Project description:Pediatric papillary thyroid carcinomas (pPTCs) are often indolent tumors with excellent long-term outcome, although subsets of cases are clinically troublesome and recur. Although it is generally thought to exhibit similar molecular aberrancies as their counterpart tumors in adults, the pan-genomic landscape of clinically aggressive pPTCs has not been previously described. In this study, five pairs of primary and synchronously metastatic pPTC from patients with high-risk phenotypes were characterized using parallel whole-genome and -transcriptome sequencing. Primary tumors and their metastatic components displayed an exceedingly low number of coding somatic mutations and gross chromosomal alterations overall, with surprisingly few shared mutational events. Two cases exhibited one established gene fusion event each (SQSTM1-NTRK3 and NCOA4-RET) in both primary and metastatic tissues, and one case each was positive for a BRAF V600E mutation and a germline truncating CHEK2 mutation, respectively. One single case was without apparent driver events and was considered as a genetic orphan. Non-coding mutations in cancer-associated regions were generally not present. By expressional analyses, fusion-driven primary and metastatic pPTC clustered separately from the mutation-driven cases and the sole genetic orphan. We conclude that pPTCs are genetically indolent tumors with exceedingly stable genomes. Several mutations found exclusively in the metastatic samples which may represent novel genetic events that drive the metastatic behavior, and the differences in mutational compositions suggest early clonal divergence between primary tumors and metastases. Moreover, an overrepresentation of mutational and expressional dysregulation of immune regulatory pathways was noted among fusion-positive pPTC metastases, suggesting that these tumors might facilitate spread through immune evasive mechanisms.
| S-EPMC8111328 | biostudies-literature
Project description:BackgroundThere is much debate on the optimal treatment approach of papillary thyroid carcinoma (PTC). Different guidelines base recommendations on various risk factors. While diagnosing the various risk factors is difficult due to the technical limitations, intraoperative frozen section (IFS) may be a feasible method. We aim to real-time evaluate the multiple risk factors, including lymph node metastasis (LNM), extrathyroidal extension (ETE), multifocality using IFS, and then identify a more effective surgical plan, which may help avoid the need for a second surgery and improve prognosis of patients.MethodsWe retrospectively reviewed the medical records of 364 patients from January 1, 2021 to December 31, 2021. All the patients were initially recommended to undergo a hemithyroidectomy (HT) with isthmusectomy and ipsilateral central compartment neck dissection (CCND). IFS would be executed immediately. Further total thyroidectomies (TTs) would be performed if: (I) results of IFS showed >5 LNM, or (II) there are 1≤ LNM ≤5 but with ETE and/or multifocal carcinoma. The patients were divided and investigated according to the extent of surgery.ResultsBased on the results of IFS, 72 patients underwent TT. The TT group displayed larger average tumor diameter, greater age, higher average body mass index (BMI), and elevated incidence of hypertension and hyperlipidemia compared to the HT group. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of IFS were 77.61%, 100%, 100%, and 88.46%, respectively.ConclusionsIFS is a highly reliable procedure. Comprehensively evaluating central compartment LNM, ETE, and multifocal carcinoma through IFS helps identify a more reasonable surgical option under the current clinical consensus, which may thus help avoid the need for a second surgery.
| S-EPMC10788568 | biostudies-literature
Project description:Background: The current American Thyroid Association risk-stratification system for papillary thyroid carcinoma (PTC) incorporates the number and size of positive lymph nodes (LNs) but places less weight on extranodal extension (ENE). This study investigated how to incorporate ENE into the current system to predict recurrence better in PTC N1 patients. Methods: A total of 369 N1 PTC patients without distant metastasis were enrolled. The combination of number of positive LNs and LNs with ENE that had the highest C-index were identified with multivariable Cox proportional hazards models. ENE number was incorporated into the current system considering the recurrence rate and unadjusted and adjusted hazard ratios (HRs) of the subgroups. Kaplan-Meier curves for recurrence based on current and alternative systems were compared by log-rank test. Results: The recurrence rate for the subgroup with five or fewer positive LNs and one to three ENEs (7/61; 11.5%) was higher than that of the subgroup with five or fewer positive LNs without ENE (5/129; 3.9%; adjusted HR = 3.42 [confidence interval (CI) 0.99-11.75]; p = 0.050). In contrast, adjusted HRs of the subgroup with more than five positive LNs and one to three ENEs (2.33 [CI 0.52-10.35]) or with four or more ENEs (3.86 [CI 1.05-14.17]) were not higher than those of the subgroup with more than five LNs without ENE (4.47 [1.16-17.19]). Incorporating ENE into the current system as an intermediate-risk group yielded a lower log-rank p-value (0.05 vs. 0.01) than the current system. Conclusions: The presence of ENE in low volume LN metastasis confers an intermediate risk of recurrence. Incorporating ENE into the current system allows more accurate decisions regarding further management of PTC N1 patients.
| S-EPMC6648218 | biostudies-literature