Papillary thyroid carcinoma with high percentage of BRAFV600E alleles have a higher recurrence rate

A. Guerra; L. Fugazzola; V. Marotta; M. Cirillo; Stasi V. Di; A. Volpe; A. Murino; Stasi M. Di; M. Vitale

P1797

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Endocrine Abstracts (2012) 29 P1797

ICEECE2012 Poster Presentations Thyroid cancer (108 abstracts)

Papillary thyroid carcinoma with high percentage of BRAFV600E alleles have a higher recurrence rate

A. Guerra ¹ , L. Fugazzola ² , V. Marotta ³ , M. Cirillo ¹ , V. Di Stasi ¹ , A. Volpe ¹ , A. Murino ¹ , M. Di Stasi ¹ & M. Vitale

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Author affiliations

¹University of Salerno, Baronissi, Salerno, Italy; ²University of Milan, Milan, Italy; ³University of Naples Federico II, Naples, Italy.

Context: Although unexplained conflicting results are present in the literature, most of studies report the association of BRAFV600E in papillary thyroid carcinoma (PTC) with a more advanced disease and with a worst prognosis. We recently demonstrated that in most of the cases PTC consists of a mixture of tumour cells with wild-type and mutant BRAF. Hence, we examined the association of percentage of BRAFV600E alleles with clinicopathologic parameters at diagnosis and disease outcome in a large series of PTC.

Study design: Tumour genotyping for BRAFV600E was performed by Big Dye Terminator and pyrosequencing in 168 patients with PTC. The association between clinicopathologic characteristics including disease recurrence at follow-up (median =5.1 years) and the percentage of BRAF mutant alleles was determined.

Results: The prevalence of BRAFV600E was higher by pyrosequencing then by Big Dye Terminator (53.6 vs 36.9%). In the PTC positive for BRAFV600E, the percentage of mutant alleles ranged 5.1–44.7% of total BRAF alleles, with a median of 20.6%. The presence or the percentage of BRAFV600E alleles did not correlate significantly with gender, multicentricity, lymph node metastasis, and tumour stage. The percentage of BRAFV600E alleles directly correlated with age at diagnosis and tumour volume (R²=0.223, P=0.039 and R²=0.166, P< 0.001 respectively). The percentage of BRAFV600E alleles (P=0.014), tumour volume (P=0.012) and lymph node metastasis (P=0.008) predicted the disease outcome. The odds ratio of recurrence in PTC with BRAFV600E alleles ≥30% was a 5.31-fold higher (P=0.002) in comparison with PTC with BRAFV600E alleles <30%.

Conclusions: High percentage of BRAFV600E alleles defines a PTC molecular subtype with a poorer disease outcome. Analysis of BRAF mutation by pyrosequencing is useful to refine the risk stratification of patients with PTC.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.