Extensive clinical experience

Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma

Cristiana Lupi, Riccardo Giannini, Clara Ugolini, Agnese Proietti, Piero Berti, Michele Minuto, Gabriele Materazzi, Rossella Elisei, Massimo Santoro, Paolo Miccoli, Fulvio Basolo

Research output: Contribution to journalArticle

293 Citations (Scopus)

Abstract

Context: Because very few studies have examined the correlation between BRAF mutations and clinicopathological features of papillary thyroid carcinoma (PTC), we analyzed here a large and homogeneous cohort of patients with PTC for the presence of the BRAF mutation. Objective: We examined BRAF mutations in a consecutive series of 500 PTC patients who underwent surgery in the Department of Surgery of the University of Pisa, and we correlated the presence of the mutation with clinicopathological parameters of the patients: age, gender, tumor size, presence of tumor capsule, extrathyroidal invasion, multicentricity, presence of node metastases, and tumor class. Design: BRAF (exon 15) mutation was examined by PCR-single strand conformational polymorphism followed by DNA sequencing in laser-capture microdissected tissue samples. Results: In this study, BRAF mutation was found in 219 of 500 cases (43.8%). In particular, we found the most common BRAF V600E mutation in 214 cases (42.8%), BRAF K601E mutation in three cases (0.6%), BRAF VK600-1E (0.2%) in one case, whereas in one case we found a new 14-bp deletion with concomitant 2-bp insertion, VKSR600-3del and T599I, respectively. BRAF V600E was associated with extrathyroidal invasion (P <0.0001), multicentricity (P = 0.0026), presence of nodal metastases (P = 0.0009), class III vs. classes I and II (P <0.00000006), and absence of tumor capsule (P <0.0001), in particular in follicular- and micro-PTC variants. By multivariate analysis, the absence of tumor capsule remained the only parameter associated (P = 0.0005) with BRAF V600E mutation. Conclusions: Our data suggest that BRAF V600E mutation is associated with high-risk PTC and in particular in follicular variant with invasive tumor growth.

Original languageEnglish
Pages (from-to)4085-4090
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number11
DOIs
Publication statusPublished - Nov 2007

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Tumors
Mutation
Capsules
Surgery
Neoplasms
Polymorphism
Papillary Thyroid cancer
Exons
Neoplasm Metastasis
Tissue
DNA Sequence Analysis
Lasers
DNA
Multivariate Analysis
Polymerase Chain Reaction
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Extensive clinical experience : Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma. / Lupi, Cristiana; Giannini, Riccardo; Ugolini, Clara; Proietti, Agnese; Berti, Piero; Minuto, Michele; Materazzi, Gabriele; Elisei, Rossella; Santoro, Massimo; Miccoli, Paolo; Basolo, Fulvio.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 11, 11.2007, p. 4085-4090.

Research output: Contribution to journalArticle

Lupi, C, Giannini, R, Ugolini, C, Proietti, A, Berti, P, Minuto, M, Materazzi, G, Elisei, R, Santoro, M, Miccoli, P & Basolo, F 2007, 'Extensive clinical experience: Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma', Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 11, pp. 4085-4090. https://doi.org/10.1210/jc.2007-1179
Lupi, Cristiana ; Giannini, Riccardo ; Ugolini, Clara ; Proietti, Agnese ; Berti, Piero ; Minuto, Michele ; Materazzi, Gabriele ; Elisei, Rossella ; Santoro, Massimo ; Miccoli, Paolo ; Basolo, Fulvio. / Extensive clinical experience : Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 11. pp. 4085-4090.
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abstract = "Context: Because very few studies have examined the correlation between BRAF mutations and clinicopathological features of papillary thyroid carcinoma (PTC), we analyzed here a large and homogeneous cohort of patients with PTC for the presence of the BRAF mutation. Objective: We examined BRAF mutations in a consecutive series of 500 PTC patients who underwent surgery in the Department of Surgery of the University of Pisa, and we correlated the presence of the mutation with clinicopathological parameters of the patients: age, gender, tumor size, presence of tumor capsule, extrathyroidal invasion, multicentricity, presence of node metastases, and tumor class. Design: BRAF (exon 15) mutation was examined by PCR-single strand conformational polymorphism followed by DNA sequencing in laser-capture microdissected tissue samples. Results: In this study, BRAF mutation was found in 219 of 500 cases (43.8{\%}). In particular, we found the most common BRAF V600E mutation in 214 cases (42.8{\%}), BRAF K601E mutation in three cases (0.6{\%}), BRAF VK600-1E (0.2{\%}) in one case, whereas in one case we found a new 14-bp deletion with concomitant 2-bp insertion, VKSR600-3del and T599I, respectively. BRAF V600E was associated with extrathyroidal invasion (P <0.0001), multicentricity (P = 0.0026), presence of nodal metastases (P = 0.0009), class III vs. classes I and II (P <0.00000006), and absence of tumor capsule (P <0.0001), in particular in follicular- and micro-PTC variants. By multivariate analysis, the absence of tumor capsule remained the only parameter associated (P = 0.0005) with BRAF V600E mutation. Conclusions: Our data suggest that BRAF V600E mutation is associated with high-risk PTC and in particular in follicular variant with invasive tumor growth.",
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AU - Ugolini, Clara

AU - Proietti, Agnese

AU - Berti, Piero

AU - Minuto, Michele

AU - Materazzi, Gabriele

AU - Elisei, Rossella

AU - Santoro, Massimo

AU - Miccoli, Paolo

AU - Basolo, Fulvio

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N2 - Context: Because very few studies have examined the correlation between BRAF mutations and clinicopathological features of papillary thyroid carcinoma (PTC), we analyzed here a large and homogeneous cohort of patients with PTC for the presence of the BRAF mutation. Objective: We examined BRAF mutations in a consecutive series of 500 PTC patients who underwent surgery in the Department of Surgery of the University of Pisa, and we correlated the presence of the mutation with clinicopathological parameters of the patients: age, gender, tumor size, presence of tumor capsule, extrathyroidal invasion, multicentricity, presence of node metastases, and tumor class. Design: BRAF (exon 15) mutation was examined by PCR-single strand conformational polymorphism followed by DNA sequencing in laser-capture microdissected tissue samples. Results: In this study, BRAF mutation was found in 219 of 500 cases (43.8%). In particular, we found the most common BRAF V600E mutation in 214 cases (42.8%), BRAF K601E mutation in three cases (0.6%), BRAF VK600-1E (0.2%) in one case, whereas in one case we found a new 14-bp deletion with concomitant 2-bp insertion, VKSR600-3del and T599I, respectively. BRAF V600E was associated with extrathyroidal invasion (P <0.0001), multicentricity (P = 0.0026), presence of nodal metastases (P = 0.0009), class III vs. classes I and II (P <0.00000006), and absence of tumor capsule (P <0.0001), in particular in follicular- and micro-PTC variants. By multivariate analysis, the absence of tumor capsule remained the only parameter associated (P = 0.0005) with BRAF V600E mutation. Conclusions: Our data suggest that BRAF V600E mutation is associated with high-risk PTC and in particular in follicular variant with invasive tumor growth.

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