The role of BRAF V600E mutation as a potential marker for prognostic stratification of papillary thyroid carcinoma: a long-term follow-up study

Abstract

Papillary carcinoma is the most prevalent malignancy of thyroid gland, and its incidence has been recently increased. The BRAF(V600E) mutation is the most frequent genetic alteration in papillary thyroid carcinoma (PTC). The role of BRAF(V600E) mutation as a potential prognostic factor has been controversially reported in different studies, with short-term follow-up. In this study, we evaluated the role of BRAF(V600E) mutation as a potential marker for prognostic stratification of patients with PTC in long-term follow-up. We studied 69 PTC patients with a mean follow-up period of 63.9 months (median: 60 m). The BRAF(V600E) mutation was analyzed by PCR-single-strand conformational polymorphism and sequencing. The correlation between the presence or absence of the BRAF(V600E) mutation, clinicopathological features and prognosis of PTC patients were studied. The BRAF(V600E) mutation was found in 28 of 69 (40.6%) PTC patients, and it was significantly more frequent in older patients (p < 0.001), in advanced tumor stages (p = 0.006) and in patients with history of radiation exposure (p = 0.037). Incomplete response to treatment in PTC patients was significantly correlated with certain clinicopathological characteristics (follow-up time, distant metastases, advanced stage, first thyroglobulin (fTg) level, history of reoperation and external radiotherapy and delay in iodine therapy) but it was not related to the presence of BRAF(V600E) mutation. Prevalence of BRAF(V600E) mutation was 40.6% in patients with papillary thyroid cancer in northeast of Iran. The BRAF(V600E) mutation was associated with older age and advanced tumor stage but was not correlated with incomplete response during follow-up.

Response to therapy of papillary thyroid cancer of known BRAF status

“…Daliri et al . (2014) analysed the relation between the BRAF V600E mutation and response to therapy in a fairly small group of 69 PTC patients.…”

Radiation and Thyroid Cancer

“…Notably, patients exposed to Chernobyl radiation developed PTC, and survivors of the atomic bomb in Japan had a very high frequency of RET/PTC chromosomal rearrangement [36]. In addiction, B-Raf proto-oncogene (BRAF) mutation (BRAF V600E) was associated with PTC [37]. Guan et al [38] demonstrated that high iodine intake was a significant risk factor for BRAF V600E mutation and the development of PTC in the thyroid gland.…”

“…Synopsis of the main literature in the field [22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45]. HLA-DR: human leukocyte antigen-DR; RET/PTC : rearranged during transfection/papillary thyroid carcinoma; PKC: protein kinase C; MAPKK7: mitogen-activated protein kinase 7; JNK: c-Jun NH2-terminal kinases; IR: ionizing radiation; UV: ultraviolet rays; ROS: reactive oxygen species.…”

The Treatment of Advanced Thyroid Cancer in the Age of Novel Targeted Therapies

“…Most agents selective for these targets remain in early phases of development, but inhibitors directed at several specific targets are reaching maturity [10–12]. The BRAF V600E mutation, which is present in a significant proportion of cases of PTC [62], is the target of the small molecule inhibitors vemurafenib and dabrafenib [39–41], which are both agents approved by the FDA for treatment of advanced melanoma harboring this mutation [20]. …”