Clinicopathological Features and Prognosis of Papillary Thyroid Microcarcinoma for Surgery and Relationships with the BRAFV600E Mutational Status and Expression of Angiogenic Factors

Shi, Chao; Guo, Yong; Lv, Yichen; Nanding, Abiyasi; Shi, Tiefeng; Qin, Huadong; He, Jianjun

doi:10.1371/journal.pone.0167414

Cited by 18 publications

(23 citation statements)

References 32 publications

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“…A previous study that analyzed the gene expression profiles of 25 pairs of thyroid microcarcinomas and normal counterparts, as well as 11 pairs of carcinomas and normal counterparts, found that the gene expression profiles of microcarcinomas were not different from those of carcinomas . Furthermore, there were no significant differences in the mRNA expression levels of pigment epithelium‐derived factor, vascular endothelial growth factor, and hypoxia‐inducible factor‐1α between high‐risk microcarcinomas and carcinomas . Our findings are in agreement with these reports.…”

Section: Discussionsupporting

confidence: 92%

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Is papillary thyroid microcarcinoma a biologically different disease? A propensity score‐matched analysis

Hsu

Lee

Chien

et al. 2019

Journal of Surgical Oncology

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Background Papillary thyroid microcarcinoma exhibits an indolent clinical course and could be a candidate for active surveillance in the appropriate setting. It remains unknown whether papillary microcarcinoma is biologically different from larger papillary carcinoma >1 cm. Methods We analyzed clinicopathological information and transcriptome data of papillary thyroid cancer samples from The Cancer Genome Atlas. Propensity‐score matching was used to construct a matched cohort consisting of 29 microcarcinomas and 58 carcinomas. Principal component analysis and unsupervised hierarchical cluster analysis were carried out to investigate the similarity of gene expression profiles. Results After adjustment for differences in baseline clinicopathological and genetic factors, transcriptome could be grouped mainly on the basis of tumor class (BRAF‐like vs RAS‐like) and tumor size (microcarcinoma vs carcinoma). The gene set enrichment analysis showed that extracellular matrix‐associated pathways were enriched in the MSigDB database. Conclusion Papillary thyroid microcarcinomas display a distinct gene expression pattern different from the corresponding carcinomas. We hypothesize that tumor microenvironment may play a role in the microcarcinoma/carcinoma phenotypic divergence.

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Section: Discussionsupporting

confidence: 92%

“…between high-risk microcarcinomas and carcinomas. 23 Our findings are in agreement with these reports. Before propensity matching, PCA revealed that microcarcinomas were virtually indistinguishable from larger carcinomas.…”

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confidence: 94%

Is papillary thyroid microcarcinoma a biologically different disease? A propensity score‐matched analysis

Hsu

Lee

Chien

et al. 2019

Journal of Surgical Oncology

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“…The worldwide incidence of thyroid cancer, especially papillary thyroid carcinoma (PTC), has increased rapidly in recent years [ 1 , 2 ]. Regional lymph node metastasis is commonly observed in PTC and occurs in approximately 30-80% of PTC patients [ 3 , 4 ], even in Papillary thyroid microcarcinoma (PTMC, ≤10 mm)[ 5 , 6 ], which may present an associated increased risk of regional recurrence and distant metastasis [ 7 ]. Previous studies reported that nodal metastasis of PTC occurs in a stepwise fashion, with metastasis beginning in the central cervical compartment, continuing to the ipsilateral cervical compartment, and finally arriving at the contralateral lateral or mediastinal compartment; therefore, the lateral compartment is the second site of PTC metastases [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Skip lateral lymph node metastasis leaping over the central neck compartment in papillary thyroid carcinoma

et al. 2017

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ObjectiveThis study was performed to investigate the frequency and pattern as well as the predictive factors of skip metastasis (lateral cervical lymph node metastasis without central lymph node metastasis) in papillary thyroid carcinoma (PTC).Methods450 PTC patients who received total thyroidectomy with central neck dissection(CND) combined with modified radical lateral neck dissection(LND) were divided into two groups: with or without skip metastases. The clinicopathological characteristics were statistically compared and analyzed, and univariate and multivariate analyses were performed to detect the risk factors of skip metastasis.ResultsThe skip metastasis rate was 8.7% (39/450), and patients with skip metastases had fewer lateral lymph node metastases but were more likely to have single-level lateral metastasis, which are considered Level II(P<0.05). Skip metastasis was significantly associated with the primary tumor location in the upper portion (OR=18.495, 95% CI 6.612-51.731), a primary tumor size ≤10mm (OR=32.492, 95% CI 11.973-88.174) and Capsule invasion (OR=5.822, 95% CI 1.954-17.343) as demonstrated by our prospective study of 10 patients who received an injection of 0.1 ml carbon nanoparticles under ultrasonography in the upper portion of the lobe: 7(70%) had lateral compartment lymph node black staining without ipsilateral center compartment lymph node staining. However, skip metastasis did not affect the PTC patients’ long-term tumor-free survival rate (P=0.432).ConclusionSkip metastases can be common, and the primary tumor location in the upper portion, a primary tumor size ≤10 mm, and capsular invasion are closely linked to skip metastasis. The lateral compartment should be carefully evaluated.

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“…BRAF gene mutation are most closely related to PTC. Studies have shown that the BRAF V600E mutation is closely related to multifocality, lymph node metastasis, extrathyroidal extension and advanced-stage of PTC, thus predictive of poor prognosis of tumours [15,16]. However, because the mutation only exists in 40-45% of PTC patients, it has some limitations as a diagnostic and prognostic marker [15].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of peripheral blood E2F3 mRNA as a potential diagnostic biomarker in human papillary thyroid cancer

Zhao¹,

Zhao²,

Wu³

et al. 2020

Preprint

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Background: The transcription factor E2F3 plays a vital role in regulating cell cycle progression and proliferation. In addition, many reports have shown that E2F3 exerts an oncogenic role in various cancers and is a promising therapeutic target for the treatment of some human cancers. However, the value of E2F3 in the molecular diagnosis and prognosis evaluation of papillary thyroid cancer (PTC) has rarely been reported. The aim of this study was to evaluate the clinical signiﬁcance of E2F3 in the early diagnosis and monitoring of PTC.Materials and methods: Peripheral blood samples from 20 patients with PTC, 20 patients with benign thyroid lesions and 20 normal controls were collected. Peripheral blood E2F3 mRNA and thyroid sample E2F3 mRNA expression were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The expression of E2F3 protein in normal thyroid tissue and thyroid tissue from benign thyroid lesions and PTC were detected by immunohistochemistry. The optimal cut-off value for differentiating PTC was obtained by using receiver operating characteristic (ROC) curve analysis.Results: E2F3 mRNA expression levels in peripheral blood and thyroid samples were significantly higher in PTC patients than in patients with benign thyroid lesions and normal subjects (P<0.05). Moreover, benign hyperplasia had higher E2F3 expression than normal tissue (P<0.01).There was no significant association between the level of E2F3 mRNA and aggressive clinicopathologic features of PTC, including TNM staging, extrathyroidal invasion, multifocality, and lymph node metastasis (P>0.05).With a cut-off value of 2.3, blood E2F3 mRNA showed 90% sensitivity, 60.9% specificity, a 70.5% positive predictive value, an 85.47% negative predictive value and 74.4% accuracy for discriminating PTC from benign hyperplasia disease of the thyroid and normal tissue. In addition, immunohistochemical results showed that E2F3 protein expression was also higher in the PTC group than in the other groups.Conclusions: The highest expression of E2F3 was found in peripheral blood and thyroid tissue of PTC patients. Moreover, blood E2F3 mRNA can be considered a promising diagnostic marker for discriminating PTC from benign thyroid diseases.

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Clinicopathological Features and Prognosis of Papillary Thyroid Microcarcinoma for Surgery and Relationships with the BRAFV600E Mutational Status and Expression of Angiogenic Factors

Cited by 18 publications

References 32 publications

Is papillary thyroid microcarcinoma a biologically different disease? A propensity score‐matched analysis

Is papillary thyroid microcarcinoma a biologically different disease? A propensity score‐matched analysis

Skip lateral lymph node metastasis leaping over the central neck compartment in papillary thyroid carcinoma

Evaluation of peripheral blood E2F3 mRNA as a potential diagnostic biomarker in human papillary thyroid cancer

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