Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAFV600E mutation

Lee, Young Ki; Park, Kyeong Hye; Park, Se Hee; Kim, Kwang Joon; Shin, Dong Yeob; Nam, Kee Hyun; Chung, Woong Youn; Lee, Mi Kyung

doi:10.1002/hed.25327

Cited by 13 publications

(8 citation statements)

References 31 publications

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“…Therefore, if serological antibody analysis is not consistent with the pathological diagnosis, we prefer the latter. On the other hand, TPOAb positivity without diffuse lymphatic invasion is not related to tumor invasiveness 36. So, antibodies were not discussed and excluded as factors in this study of prognostic factors associated with PTC.…”

Section: Discussionmentioning

confidence: 94%

Upregulation Of Protein Tyrosine Phosphatase Receptor Type C Associates To The Combination Of Hashimoto’s Thyroiditis And Papillary Thyroid Carcinoma And Is Predictive Of A Poor Prognosis

Han

Vladimirovna

et al. 2019

OTT

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IntroductionPTC is not generally considered a lethal disease, but prone to recurrence as the prognosis. Hashimoto’s thyroiditis (HT) is an important factor that affects the prognosis of papillary thyroid carcinoma (PTC). It is crucial to find biomarkers to identify the combination of HT with PTC and to predict the prognosis.MethodsRNASeq data from the Cancer Genome Atlas (TCGA) database was used to screen differentially expressed genes (DEGs) of PTC with HT via the edgeR package of R software version 3.3.0. Also, the DEGs were applied to the DAVID web-based tool to determine the enrichment of gene functions via Gene Ontology (GO) analysis and to identify associated pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. By constructing protein interaction networks within Cytoscape software, we screened candidate genes and explored possible relationships with the clinical phenotype of PTC. Finally, additional thyroid tissue samples were collected to verify the results above.ResultsAfter analyzing the RNA-Seq data of PTC patients from the Cancer Genomic Atlas, 497 differentially expressed PTC genes were found to be associated with HT, of which protein tyrosine phosphatase receptor type C (PTPRC), KIT, and COL1A1 were associated with tumor size and lymph node metastasis (p < 0.05). Verification of these results with another 30 thyroid tissues of clinical PTC patients revealed that the expression level of PTPRC in the PTC with HT group was higher than that in the PTC without HT group (p < 0.05) and the ROC curve showed a good discrimination (area under the curve = 0.846). However, the correlation with the clinical phenotype was not statistically significant (p > 0.05).DiscussionThese data suggest that upregulation of PTPRC enhances the incidence of HT associated with PTC and is also predictive of a poor prognosis.

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Section: Discussionmentioning

confidence: 94%

Upregulation Of Protein Tyrosine Phosphatase Receptor Type C Associates To The Combination Of Hashimoto’s Thyroiditis And Papillary Thyroid Carcinoma And Is Predictive Of A Poor Prognosis

Han

Vladimirovna

et al. 2019

OTT

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“…TPOAb are also found to be associated with the absence of distant metastases in patients with newly diagnosed breast cancer ( 33 ). Lee et al ( 17 ) suggested that diffuse lymphocytic infiltration was associated with aggressive features in PTC when TPOAb was negative, but tend to be indolent when TPOAb was positive. However, in the present study, both univariate and multivariate Logistic Regression analyses failed to identify the effect of TPOAb+ and/or TgAb+ status, or even extremely high levels of TPOAb or TgAb, on LNM of thyroid cancer.…”

Section: Discussionmentioning

confidence: 99%

“…There is accumulating evidence that Hashimoto's thyroiditis (HT) is associated with increased risk of thyroid cancer (14)(15)(16). While the role of HT in LNM in patients with thyroid cancer remains conflicting (15,17,18). Although HT has been reported for not influencing the risk of recurrence in patients with PTC (19), there are also several studies demonstrated that HT is associated with less aggressiveness and tend to be a protective factor for LNM (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Thyroid antibody status exerts insignificant effect on lymph node metastasis of thyroid cancer

Zhou¹,

Zhiqiang²,

Zhou³

et al. 2020

Transl Cancer Res TCR

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Background: To investigate whether high thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels are associated with increased risk of lymph node metastasis (LNM) of thyroid cancer. Methods: Data of 2,352 patients who committed thyroidectomy from January 2018 to December 2018 at our institution were retrospectively reviewed. Of which, 806 patients diagnosed with thyroid cancer with available data of both TPOAb and TgAb were finally included, and were divided into four groups: (I) TPOAb−/TgAb− (control, n=493), (II) TPOAb+/TgAb− (n=96), (III) TPOAb−/TgAb+ (n=104), and (IV) TPOAb+/TgAb+ (n=113). The demographic and clinicopathological data were analyzed.Results: Compared to control, significantly less extrathyroidal invasions were identified in TPOAb+ and/or TgAb+ patients (P<0.05), while no significant differences for tumor size, multifocality, or central/lateral neck LNM rate were found for TPOAb+ and/or TgAb+ groups (all P>0.05). Compared to control, significantly more lymph nodes were removed during neck dissection (P<0.05), but there were no significant differences for the number or size of lymph nodes involved (all P>0.05) for TPOAb+ and/or TgAb+ patients. TPOAb+ and/or TgAb+ were not identified as risk factors or protect factors of LNM of thyroid cancer in Logistic regression analyses. Conclusions:In the present study, we demonstrated that anti-thyroid peroxidase and thyroglobulin antibodies are not associated with increased risk of lymph node metastasis of thyroid cancer.

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“…In recent years, thanks to the expansion of knowledge on the molecular, genetic, and epigenetic aspects of thyroid cancer, research has aimed to specifically profile tumors with more aggressive behavior and/or resistance to therapy [22]. Immune tumor microenvironment [23, 24], epithelial-mesenchymal transition [25–28], and some peculiar features including BRAF V600E mutation [29], TERT promoter mutations [30, 31], and transcriptomic signatures [32, 33] have been described as predictors of aggressive DTC. Moreover, several serum or tissue miRNAs (either upregulated or downregulated) have been reported to be involved in DTC initiation, progression, and aggressiveness [34, 35].…”

Section: Discussionmentioning

confidence: 99%

PSMA expression level predicts differentiated thyroid cancer aggressiveness and patient outcome

et al. 2019

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Background Prostate-specific membrane antigen (PSMA) is overexpressed on the endothelial cells of tumor neo-vessels of several solid malignancies, including differentiated thyroid cancer (DTC). We aimed to test the potential role of PSMA as a biomarker for DTC aggressiveness and outcome prediction. We retrospectively screened all patients who underwent thyroidectomy between 1 January 2010 and 31 December 2017 in our institution. Applying the inclusion (histological diagnosis of thyroid cancer and tissue availability) and exclusion criteria (no clinical or follow-up data or diagnosis of medullary thyroid cancer), a cohort of 59 patients was selected. The monoclonal mouse anti-human PSMA antibody was used to stain tissue sections. A 3-point scale was used to score PSMA positivity: 0–5% expression was considered as negative (score 0), 6–50% as moderately positive (score 1), and 51–100% as highly positive (score 2). A cumulative score (0–10%, 11–79%, and 80–100%) was also explored. Univariate and multivariate logistic regression analyses were performed to predict the presence of distant metastases, chosen as endpoint of aggressiveness. The area under the curve (AUC) was calculated. Cox models were built to predict patient outcome in terms of recurrence, iodine refractoriness, and status at last follow-up, which were calculated using the Kaplan-Meier failure function. Results At immunostaining, 12, 25, and 22 patients had scores of 0, 1, and 2, respectively. According to the cumulative score, PSMA expression was ≤ 10% in 17 cases, 11–79% in 31 cases, and ≥ 80% in 11 cases. At multivariate analysis, age, sex, histotype, vascular invasion, T and N parameters, and PSMA positivity were significant predictors of distant metastases. The AUC was 0.92. Recurrence or progression occurred in 19/59 patients. Twelve patients developed radioiodine (RAI) refractoriness, after a median time of 17 months (range 2–32). One patient died of DTC; 46 of the 58 patients alive at last follow-up were disease free. Median DFS was 23 months (range 3–82). The final multivariate model to predict RAI refractoriness included as covariates the stage, high PSMA expression (≥ 80%), and the interaction between moderate PSMA expression (11–79%) and stage. Conclusions PSMA, a marker of neovasculature formation expressed by DTC, contributes in the prediction of tumor aggressiveness and patient outcome.

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Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAF^V600E mutation

Cited by 13 publications

References 31 publications

<p>Upregulation Of Protein Tyrosine Phosphatase Receptor Type C Associates To The Combination Of Hashimoto’s Thyroiditis And Papillary Thyroid Carcinoma And Is Predictive Of A Poor Prognosis</p>

<p>Upregulation Of Protein Tyrosine Phosphatase Receptor Type C Associates To The Combination Of Hashimoto’s Thyroiditis And Papillary Thyroid Carcinoma And Is Predictive Of A Poor Prognosis</p>

Thyroid antibody status exerts insignificant effect on lymph node metastasis of thyroid cancer

PSMA expression level predicts differentiated thyroid cancer aggressiveness and patient outcome

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