The role of BRAF(V600E) mutation as poor prognostic factor for the outcome of patients with intrathyroid papillary thyroid carcinoma.

BACKGROUND: BRAF(V600E) mutation, which represents the most frequent genetic mutation in papillary thyroid carcinoma (PTC), is widely considered to have an adverse outcome on PTC outcome, however its real predictive value is not still well stated. The aim of the present study was to evaluate if BRAF(V600E) mutation could be useful to identify within patients with intrathyroid ultrasound-N0 PTC those who require more aggressive treatment, by central neck node dissection (CLND) or subsequent postoperative (131)I treatment. METHODS: Among the whole series of 931 consecutive PTC patients operated on at 2nd Clinical Surgery of University of Padova and at General Surgery Department of University of Trieste during a period from January 2007 to December 2012, we selected 226 patients with an intrathyroid tumor and no metastases (preoperative staging T1-T2, N0, M0). BRAF(V600E) mutation was evaluated by PCR-single-strand conformation polymorphism analysis and direct genomic sequencing. We analyzed the correlation between the presence/absence of the BRAF(V600E) mutation in the fine-needle aspiration (FNA) and the clinical-pathological features: age, gender, extension of surgery, node dissection, rate of cervical lymph node involvement, tumor size, TNM stage, variant of histotype, mono/plurifocality, association with lymphocitary chronic thyroiditis, radioactive iodine ablation doses, and outcome. RESULTS: The BRAF(V600E) mutation was present in 104 of 226 PTC patients (47.8%). BRAF(V600E) mutation correlated with multifocality, more aggressive variants, infiltration of the tumoral capsule, and greater tumor's diameter. BRAF(V600E) mutation was the only poor prognostic factor in these patients. DISCUSSION: In our series, BRAF(V600E) mutation demonstrated to be an adverse prognostic factor indicating aggressiveness of disease and it could be useful in the management of low-risk PTC patients, as supplementary prognostic factor to assess the preoperative risk stratification with the aim to avoid unnecessary central neck node dissection (BRAF pos.) or to perform complementary (131)I-therapy (BFAF neg.).

Diagnosis, treatment, prognostic factors and long-term outcome in papillary thyroid carcinoma.

The papillary thyroid carcinoma (PTC) is the most frequent endocrine cancer and it is the most common thyroid cancer (85-95%). Potential risk factors for the incidence of the PTC include radiation exposure, iodine deficiency, family history of thyroid cancer. The PTC is usually indolent and the prognosis is favourable, with a 10 year survival generally reported to exceed 90%. The palpation and growth of thyroid nodules are the more frequent clinical manifestations of the PTC which can be evaluated by physical examination, neck ultrasound and fine needle aspiration cytology (FNAC). The therapeutic management of PTC includes surgical treatment combined with 131I therapy and life long TSH suppressive thyroid hormone replacement. The external beam radiation can be taken into account in select aggressive tumours. Nevertheless the good prognosis of the PTC, the prevalence of persistence or recurrent disease is not trans-curable. The biomolecular studies can permit to individuate the more aggressive PTC subtypes. A more significant attention of the clinical examination, US and FNAC to the thyroid nodular disease will be able to guarantee a more precocious diagnosis and a radical surgical treatment.

[Papillary thyroid microcarcinoma. Long-term outcome in 587 cases compared with published data]. / Il microcarcinoma papillare della tiroide: nostra esperienza e letteratura a confronto.

AIM: Papillary thyroid microcarcinoma (PTMC), a tumor measuring =or<1 cm according to the World Health Organization (WHO) histologic classification, is the most common histologic variant of thyroid cancer. The aim of this study was to evaluate the long-term outcome of surgical treatment for PTMC at a single institution with a view to differentiate therapy options based on risk of progression of disease by comparing our results with those reported in the literature. METHODS: The study sample was a total of 587 cases of PTMC treated surgically at our institution between 1990 and 2006. PTMC was an incidental finding (PTMC-I) in 325 (55.4%) cases, diagnosed preoperatively (PTMC-D) at echography and needle-aspiration biopsy in 229 (39%), and occult with metastasis (PTMC-O) in 33 (5.6%). Patients were grouped into two classes (PTMC diameter =or>5 mm or <5 mm) and compared against prognostic factors: sex, age, type of PTMC (PTMC-I, PTMC-D, PTMC-O), extent of surgery, lymph node dissection, lymph node metastasis, iodine-131 (131-I) therapy, state of disease, relapses. These parameters were then compared against tumor size (PTMC diameter =or>5 mm or <5 mm), excluding cases of PTMC-O with metastasis. RESULTS: Comparison of the two groups divided by tumor size, across the entire sample and after PTMC-O cases were excluded, revealed significant differences in the type of PTMC, frequency of partial thyroidectomy, presence of lymph node metastasis, iodine-131 therapy, life status and recurrence rate. CONCLUSION: Published PTMC studies were analyzed for definition of the disease, incidence, therapy, prognosis, and follow-up results and compared with our data. The results of our analysis argue against use of the term ''microcarcinoma'' in the wider sense since the three PTMC categories (PTMC-I, PTMC-D, PTMC-O) present different behaviour patterns. When cases of PTMC-O with clinically manifest metastasis were excluded, none of the patients with PTMC <5 mm in diameter were reoperated for tumor recurrence and all are currently free of disease. In conclusion In PTMC <5 mm in diameter, whether PTMC-I and PTMC-D, and without evidence of lymph node involvement, partial thyroidectomy may be a viable approach to treatment. By contrast, occult PTMC with metastasis is prognostically important and should therefore be treated like tumors =or>5 mm in diameter.