BRAFV600E mutation and p27kip1 expression in papillary carcinomas of the thyroid ≤1 cm and their paired lymph node metastases

Rodolico, Vito; Cabibi, Daniela; Pizzolanti, Giuseppe; Richiusa, Pierina; Gebbia, Nicola; Martorana, Annamaria; Russo, Antonio; Amato, Marco; Galluzzo, Aldo; Giordano, Carla

doi:10.1002/cncr.22912

Cited by 78 publications

(73 citation statements)

References 25 publications

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“…In our previous work, BRAF V600E mutation was evaluated in a series consecutive of patients by a real-time, allele-specific amplification essentially as described by Jarry et al 21,22 Here we randomly selected 27 patients from the described group. Age of the 27 patients who underwent surgery for the classical variant of papillary thyroid carcinoma ranged from 17 to 76 years (median age was 48 years), and there was a strong predominance of female patients (81%).…”

Section: Case Selectionmentioning

confidence: 99%

BRAF mutation influences hypoxia-inducible factor-1α expression levels in papillary thyroid cancer

et al. 2010

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Hypoxia-inducible factor-1a is found frequently overexpressed in solid tumors cells, exerting an important role in angiogenesis, glucose metabolism, cell proliferation, survival and invasion. In thyroid carcinomas, hypoxiainducible factor-1a expression was found increased in differentiated, poorly differentiated, medullary and anaplastic variants. Hypoxia represents the principal stimulus responsible for hypoxia-inducible factor-1a induction. Other nonhypoxic stimuli increase hypoxia-inducible factor-1a synthesis through the activation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in a cell-type-specific manner. We have previously shown the role of BRAF V600E mutation in papillary thyroid cancer cells as a factor that facilitates tumor cell growth and progression. In this study, we tested the hypothesis that BRAF V600E mutation influences hypoxia-inducible factor-1a expression in papillary thyroid carcinoma cells. We analyzed 27 papillary thyroid carcinomas, 13 of which presented BRAF V600E mutation. In tumor tissues, immunoreactivity for hypoxiainducible factor-1a was detected in the majority of analyzed BRAF V600E mutated cases. Transcriptional analyses revealed elevated hypoxia-inducible factor-1a levels with significant differences between wild-type and mutated group. A BRAF wild-type papillary thyroid carcinoma cell line and a BRAF V600E mutated papillary thyroid carcinoma cell line were selected to study the effects of BRAF mutation on hypoxia-inducible factor-1a expression in vitro. Knockdown of mutant BRAF V600E or both the wild type and the BRAF V600E by RNA interference induced a significant reduction of hypoxia-inducible factor-1a expression at mRNA and protein levels. Pharmacological inhibition of BRAF significantly reduces hypoxia-inducible factor-1a expression levels in papillary thyroid carcinoma cell line harboring BRAF V600E mutation. Our results suggest that hypoxiainducible factor-1a is expressed in papillary thyroid carcinomas and is regulated not only by hypoxia but also by BRAF V600E -mediated signaling pathway.

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Section: Case Selectionmentioning

confidence: 99%

BRAF mutation influences hypoxia-inducible factor-1α expression levels in papillary thyroid cancer

et al. 2010

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“…At variance with RET/ PTC, BRAF (V600E) positive PTCs were not found to be in relationship to previous radiation exposure (Nikiforova et al 2004); no other environmental factors has been identified that favors BRAF (V600E) mutation. Several studies tried to establish a correlation between BRAF (V600E) and the clinical features of PTCs, but results have been controversial (Lee et al 2007, Xing 2007: in some studies, BRAF (V600E) was associated with a more advanced tumor or a more aggressive phenotype (Namba et al 2003, Nikiforova et al 2003, Kim et al 2004, 2006a,b, Oler et al 2005, Powell et al 2005, Jin et al 2006, Riesco-Eizaguirre et al 2006, Kebebew et al 2007, Rodolico et al 2007, while other studies did not find this association (Fugazzola et al 2004, Puxeddu et al 2004, Kim et al 2005, Liu et al 2005, Trovisco et al 2005, Jo et al 2006, Park et al 2006, Sapio et al 2006, Abrosimov et al 2007, Durante et al 2007, Mitsiades et al 2007; see Table 1). Kim et al (2006a) 203 Korea Kim et al (2006b) 103 USA (CA) 100 Korea Riesco-Eizaguirre et al…”

Section: Introductionmentioning

confidence: 99%

“…67 Spain Giannini et al (2007) 69 Italy Kebebew et al (2007) 274 USA (CA) Lupi et al (2007) 500 Italy Rodolico et al (2007) Discrepancies between those studies, however, may depend on heterogeneous series of tumors, including different PTC variants and tumors from different geographical areas (Lee et al 2007, Xing 2007. BRAF (V600E) is also the most common genetic alteration occurring in micro-PTCs (w30-50% of cases; Sedliarou et al 2004, Barbaro et al 2005, Trovisco et al 2005.…”

Section: Introductionmentioning

confidence: 99%

BRAF(V600E) mutation and the biology of papillary thyroid cancer

Frasca¹,

Nucera²,

Pellegriti³

et al. 2008

Endocrine Related Cancer

212

170

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“…Several studies have shown the positive relationship between BRAF V600E mutation and other aggressive factors, such as extrathyroidal extension, LNM, high TNM stages, and recurrence [11][12][13]. Thus, BRAF V600E mutation is considered as a powerful biomarker for predicting poor prognosis.…”

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The synergic effect of BRAFV600E 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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BRAF^V600E mutation and p27^kip1 expression in papillary carcinomas of the thyroid ≤1 cm and their paired lymph node metastases

Cited by 78 publications

References 25 publications

BRAF mutation influences hypoxia-inducible factor-1α expression levels in papillary thyroid cancer

BRAF mutation influences hypoxia-inducible factor-1α expression levels in papillary thyroid cancer

BRAF(V600E) mutation and the biology of papillary thyroid cancer

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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