Multifocal Papillary Thyroid Cancer Increases the Risk of Central Lymph Node Metastasis

A, Al Afif; Ba, Williams; Mh, Rigby; Mj, Bullock; Sm, Taylor; Trites, Jonathan; Rd, Hart

doi:10.1089/thy.2015.0130

Cited by 100 publications

(85 citation statements)

References 30 publications

(16 reference statements)

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“…It is important to consider multifocality when deciding on the extent of surgical therapy, because it is a sign of tumor aggressiveness and is associated with an increased risk of lymph node metastasis and recurrent disease. 11,[33][34][35] This is also found in our series, where 42% (n 5 5) of the patients with a multifocal tumor had tumor invasion outside the thyroid.…”

Section: Histopathological Characteristicssupporting

confidence: 83%

Maternal and obstetrical outcome in 35 cases of well‐differentiated thyroid carcinoma during pregnancy

et al. 2017

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Section: Histopathological Characteristicssupporting

confidence: 83%

Maternal and obstetrical outcome in 35 cases of well‐differentiated thyroid carcinoma during pregnancy

et al. 2017

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“…The role of multifocality as a risk factor for a more severe clinical course is controversial. However, several reports have suggested multifocality status as a poor prognostic factor (38,39). In the present analysis of individual SNPs, only one variant (rs2439302) displayed significant association with multifocality.…”

Section: Discussioncontrasting

confidence: 49%

Papillary Thyroid Carcinoma: Association Between Germline DNA Variant Markers and Clinical Parameters

Jendrzejewski

Liyanarachchi

Nagy

et al. 2016

Thyroid

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Background: Papillary thyroid cancer (PTC) is reported to be highly heritable in epidemiological studies. Genome-wide association studies (GWAS) have uncovered several variants associated with PTC predisposition. It remains unknown whether these variants might contribute to better clinical stratification of PTC patients. Methods: In order to assess the usefulness of germline genetic analyses in the management of PTC patients, the genotypes of five variants (rs965513, rs944289, rs116909374, rs2439302, and rs966423) were determined in 1216 PTC patients and 1416 controls. Additionally, the expression of seven genes located close to GWAS variants (PTCSC3, MBIP, NKX2-1, FOXE1, DIRC3, PTCSC2, and NRG1) were measured in 73 PTC paired tumor/normal tissues, respectively. Next, the association was analyzed between the genotypes of the germline variants and the levels of gene expression with clinical/pathological features such as age, sex, TNM staging, multifocality status, extrathyroidal expansion, and MACIS score. Results: The risk allele of rs965513 was associated with larger tumor size ( p = 0.025) and extrathyroidal expansion (odd ratio [OR] = 1.29, p = 0.045). The variant rs2439302 showed association with lymph node metastasis (OR = 1.24, p = 0.016), and multifocality status of the tumor (OR = 1.24, p = 0.012). The expression of MBIP was associated with T stage ( p = 0.010). MBIP and PTCSC3 displayed lower expression in PTC tissue in males than in females ( p = 0.025 and p = 0.036, respectively). NKX2-1 displayed lower expression in patients with N1 stage ( p = 0.040). Conclusions: The studied germline risk alleles predisposing to PTC were associated with a more aggressive course of the disease reflected by larger tumor diameter, higher multifocality rate, and more advanced N stage at the time of diagnosis. These results show that germline variants not only predispose to PTC but also might impact its clinical course. However, these associations were only moderate, and further large multi-ethnic studies are required to evaluate the usefulness of these germline variants in the clinical stratification of PTC patients.

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“…In this study, the incidence of BRAF V600E mutation was 50.6%, which was consistent with those in other studies. In terms of multifocality, it was considered as an independent factor for CLNM [15]. For this study, we compared clinicopathological factors in the patients with and without CLNM through univariate and multivariate analysis firstly.…”

Section: Discussionmentioning

confidence: 99%

“…Multifocality also frequently exhibits in PTC. Certain studies have indicated that multifocal carcinoma in PTC is positively associated with the incidence of CLNM [14,15], while other studies have argued that there is no association between multifocality and CLNM [16]. In addition, multifocality has found to significantly increase the incidence of recurrence [17].…”

mentioning

confidence: 99%

The synergic effect of BRAF<sup>V600E</sup> mutation and multifocality on central lymph node metastasis in unilateral papillary thyroid carcinoma

Qu¹,

Hu³

et al. 2018

Endocr J

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Abstract. The purpose of this study is to evaluate the potential synergic effect of BRAF V600E mutation and multifocality on central lymph nodes metastasis (CLNM) in the patients with unilateral papillary thyroid carcinoma (PTC). We enrolled 413 patients with unilateral PTCs who accepted prophylactic unilateral or bilateral central lymph node dissection (LND). Univariate and multivariate analyses were made to determine the association between related factors and CLNM. Then, all patients were divided into 4 groups based on their status of BRAF V600E mutation and multifocality. Relative excess risk of interaction (RERI), attributable proportion (AP) of interaction and synergy index (SI) were applied to evaluate the interactive effect of these two factors on CLNM. Results showed that BRAF V600E mutation and multifocality were independent risk factors for CLNM. A further study revealed that unilateral PTCs accompanying multifocality with BRAF V600E mutation had the highest incidence of CLNM compared with other subgroups. Besides, RERI was 4.323 (95% CI = 1.276-7.369), AP was 0.523 (95% CI = 0.364-0.682) and SI was 2.469 (95% CI = 1.607 to 3.794), indicating a significant additive interaction of BRAF V600E mutation and multifocality on CLNM. The present study has confirmed that BRAF V600E mutation and multifocality are risk factors for CLNM in unilateral PTC. Additionally, unilateral PTC patients accompanying multifocality with BRAF V600E mutation may have an increased risk of CLNM in clinically negative CLNM.

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Multifocal Papillary Thyroid Cancer Increases the Risk of Central Lymph Node Metastasis

Abstract: There is a significant association between multifocal PTC and level VI lymph node positivity, increasing proportionally with the number of foci. These findings recognize multifocality as a sign of tumor aggressiveness, as evidenced by a higher propensity for lymph node metastasis.

Cited by 100 publications

References 30 publications

Maternal and obstetrical outcome in 35 cases of well‐differentiated thyroid carcinoma during pregnancy

Maternal and obstetrical outcome in 35 cases of well‐differentiated thyroid carcinoma during pregnancy

Papillary Thyroid Carcinoma: Association Between Germline DNA Variant Markers and Clinical Parameters

The synergic effect of BRAF<sup>V600E</sup> mutation and multifocality on central lymph node metastasis in unilateral papillary thyroid carcinoma

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