No correlation between BRAF<sup>V600E</sup> mutation and clinicopathological features of papillary thyroid carcinomas in Taiwan

Liu, Rue Tsuan; Chen, Yi Ju; Chou, Fong‐Fu; Li, Chunliang; Wu, Wei; Tsai, Po Chin; Huang, Chao; Cheng, Jiin Tsuey

doi:10.1111/j.1365-2265.2005.02367.x

Cited by 126 publications

(102 citation statements)

References 32 publications

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“…The most prevalent subgroup of classical and follicular variants of PTC showed no association of BRAF mutation with poor prognostic factors or poor outcome. Our findings corroborated recent studies (20,21,22,23) and also discarded the association of p.V600E with higher frequency of cervical LN and distant metastases (13,24,25,26). In order to justify the lack of association, it has also been proposed that it is not the intratumoral presence of BRAF mutation that determines prognosis but the higher frequency of mutant BRAF alleles, identified in an innovatory analysis of pyrosequencing technique, that favors more frequent recurrence (27).…”

Section: Clinical Study D L S Danilovic and Others Preoperative Molecsupporting

confidence: 80%

Pre-operative role of BRAF in the guidance of the surgical approach and prognosis of differentiated thyroid carcinoma

Danilovic

Lima

Domingues

et al. 2014

European Journal of Endocrinology

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Objective: The p.V600E BRAF and RAS mutations are found in 30-80% of differentiated thyroid carcinoma (DTC). BRAF mutation has been associated with poor prognosis. This study investigated the role of molecular studies in preoperative diagnosis of DTC and the association of p.V600E mutation with prognostic factors. Design: Prospective study. Methods: A total of 202 patients with cytological diagnosis of Bethesda III-VI underwent preoperative molecular studies and subsequent thyroidectomy. p.V600E and RAS mutations were studied in the cytology smears, using real-time PCR genotyping technique. The BRAF mutation (BRAF C or BRAF K ) was correlated with histological and clinical findings. Results: Molecular study of 172 nodules with Bethesda III-V cytology improved negative predictive value and accuracy of Bethesda III and IV diagnosis. BRAF mutation was present in 65% of 94 DTC and p.Q61R NRAS in one. Except for age, BRAF C and BRAF K did not differ in sex, tumor size, histological subtype, multifocality, vascular invasion, extrathyroidal extension, or prognostic staging. Among papillary carcinomas, lymph node (LN) metastasis was diagnosed in 23% BRAF C and 37% BRAF K . Distant metastasis occurred in four BRAF K . Recurrent or persistent disease was more frequent in BRAF K (26.7 vs 3.3% BRAF C , PZ0.002) along follow-up of 29.8G10 months. BRAF C patients without LN metastasis by pre-operative evaluation submitted to thyroidectomy with central neck dissection (CND) had more frequent LN metastasis (45 vs 5% no CND, PZ0.002), but no difference in clinical outcome was observed. Conclusions: Pre-operative identification of BRAF mutation improved cytological diagnosis of DTC, but it was not associated with poor prognostic factors. Prophylactic CND did not guarantee better outcome in BRAF C patients.

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Section: Clinical Study D L S Danilovic and Others Preoperative Molecsupporting

confidence: 80%

Pre-operative role of BRAF in the guidance of the surgical approach and prognosis of differentiated thyroid carcinoma

Danilovic

Lima

Domingues

et al. 2014

European Journal of Endocrinology

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“…These results are in agreement with those reported in other series (Kim et al 2005, Liu et al 2005, Trovisco et al 2005. On the contrary, previous data on the association of B-RAF with a worse stage and/or local or distant metastases or recurrence (Namba et al 2003, Xing 2005 are not confirmed in the present large series.…”

Section: Discussioncontrasting

confidence: 52%

“…At present, no other unequivocal correlations between genotype and clinico-pathologic features of PTC patients have been reported both in previous reports from the present authors (Fugazzola et al 2004, Puxeddu et al 2004) and in other more recent studies (Sedliarou et al 2004, Kim et al 2005, Liu et al 2005, Trovisco et al 2005. A few studies (Namba et al 2003, Xing 2005 have shown a correlation of B-RAF V600E with more advanced stage, nodal/distant metastases at diagnosis or tumor recurrence.…”

Section: V600ementioning

confidence: 66%

Correlation between B-RAFV600E mutation and clinico–pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature

Fugazzola¹,

Puxeddu²,

Avenia³

et al. 2006

Endocr Relat Cancer

216

181

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Recently, a somatic point mutation of the B-RAF gene (V600E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC), with a prevalence variable among different series. Since discordant data on the clinico-pathologic features of B-RAF mutated PTC are present in the literature, the aim of the present co-operative study was to establish the prevalence of this genetic alteration and to perform a genotype-phenotype correlation in a large cohort of patients with PTC. To this purpose, a series of 260 sporadic PTCs with different histological variants were included in the study. The mutational analysis of the B-RAF gene was performed either by RT-PCR followed by single-stranded conformational polymorphism or by PCR and direct sequencing. Statistical analyses were obtained by means of 2 /Fisher's exact test and t-test. Overall, a heterozygous T > A transversion at nucleotide 1799 (V600E) was found in 99 out of 260 PTCs (38%). According to the histological type of the tumor, the B-RAF V600E mutation was present in 48.3% of cases of classic PTCs (85 out of 176), in 17.6% (nine out of 51) of follicular variants of PTCs, in 21.7% (five out of 23) in other PTC variants and in none of the ten poorly differentiated tumors. B-RAF V600E was significantly associated with the classic variant of PTC (P ¼ 0:0001) and with an older age at diagnosis (P ¼ 0:01). No statistically significant correlation was found among the presence of B-RAF V600E and gender, tumor node metastasis (TNM), multicentricity of the tumor, stage at diagnosis and outcome. In conclusion, the present study reports the prevalence of B-RAF V600E (38%) in the largest series of sporadic PTCs, including 260 cases from three different Italian referring centers. This prevalence is similar to that calculated by pooling together all data previously reported, 39.6% (759 out of 1914 cases), thus indicating that the prevalence of this genetic event lies around 38-40%. Furthermore, B-RAF V600E was confirmed to be associated with the papillary growth pattern, but not with poorer differentiated PTC variants. A significant association of B-RAF mutation was also found with an older age at diagnosis, the mutation being very rare in childhood and adolescent PTCs. Finally, no correlation was found with a poorer prognosis and a worse outcome after a median follow-up of 72 months.

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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%

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

Frasca¹,

Nucera²,

Pellegriti³

et al. 2008

Endocrine Related Cancer

211

170

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No correlation between BRAF^V600E mutation and clinicopathological features of papillary thyroid carcinomas in Taiwan

Abstract: BRAFV600E mutation is the most prevalent oncogene in PTCs in Taiwan. Our data did not suggest that BRAFV600E mutation could be a potentially useful marker of prognosis in patients with papillary carcinomas in the population studied.

Cited by 126 publications

References 32 publications

Pre-operative role of BRAF in the guidance of the surgical approach and prognosis of differentiated thyroid carcinoma

Pre-operative role of BRAF in the guidance of the surgical approach and prognosis of differentiated thyroid carcinoma

Correlation between B-RAFV600E mutation and clinico–pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature

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

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No correlation between BRAFV600E mutation and clinicopathological features of papillary thyroid carcinomas in Taiwan

Abstract: BRAFV600E mutation is the most prevalent oncogene in PTCs in Taiwan. Our data did not suggest that BRAFV600E mutation could be a potentially useful marker of prognosis in patients with papillary carcinomas in the population studied.

Cited by 126 publications

References 32 publications

Pre-operative role of BRAF in the guidance of the surgical approach and prognosis of differentiated thyroid carcinoma

Pre-operative role of BRAF in the guidance of the surgical approach and prognosis of differentiated thyroid carcinoma

Correlation between B-RAFV600E mutation and clinico–pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature

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

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No correlation between BRAF^V600E mutation and clinicopathological features of papillary thyroid carcinomas in Taiwan