Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas

Abstract

Screening of REarranged during Transfection (RET) gene mutations has been carried out in different series of sporadic medullary thyroid carcinomas (MTC). RET-positive tumours seem to be associated to a worse clinical outcome. However, the correlation between the type of RET mutation and the patients' clinicopathological data has not been evaluated yet. We analysed RET exons 5, 8, 10 -16 in fifty-one sporadic MTC, and found somatic mutations in thirty-three (64.7%) tumours. Among the RET-positive cases, exon 16 was the most frequently affected (60.6%). Two novel somatic mutations (Cys630Gly, c.1881del18) were identified. MTC patients were divided into three groups: group 1, with mutations in RET exons 15 and 16; group 2, with other RET mutations; group 3, having no RET mutations. Group 1 had higher prevalence (P ¼ 0.0051) and number of lymph node metastases (P ¼ 0.0017), and presented more often multifocal tumours (P ¼ 0.037) and persistent disease at last control (P ¼ 0.0242) than group 2. Detectable serum calcitonin levels at last screening (P ¼ 0.0119) and stage IV disease (P ¼ 0.0145) were more frequent in group 1, than in the other groups. Our results suggest that, among the sporadic MTC, cases with RET mutations in exons 15 and 16 are associated with the worst prognosis. Cases with other RET mutations have the most indolent course, and those with no RET mutations have an intermediate risk.

Elevated level of serum carbohydrate antigen 19.9 as predictor of mortality in patients with advanced medullary thyroid cancer

“…We know that the presence of RET somatic mutations correlates with an advanced stage at the time of diagnosis and a lower survival rate (11,12,13). In the present series, the RET somatic mutations did not correlate with the death of these patients.…”

“…Advanced age at diagnosis, advanced stage of the disease and, in particular, the presence of distant metastasis at the time of diagnosis have been found to be correlated with a worse prognosis (6,7,8,9). RE-arranged during transfection (RET) somatic mutations, which are present in 40-50% of sporadic MTC patients, have also been recognized as a poor prognostic factor for the outcome of these patients (10,11,12,13).…”

Combined RET and Ki-67 assessment in sporadic medullary thyroid carcinoma: a useful tool for patient risk stratification

“…In particular, somatic RET mutations and/or RET polymorphisms were analyzed in several series of sporadic MTC, and RET status was found to correlate with patient outcome (10)(11)(12). Recent reports have demonstrated that somatic RET mutations occur in 30-50% of sporadic cases of MTC, and they are a negative predictor of cancer remission and survival (13)(14)(15). Such reports were not always homogeneous in terms of the frequency, type, and site of somatic RET mutations, or their association with clinical and pathological features, suggesting that other biological markers could also be useful for ascertaining a patient's risk.…”

Characterization of Wild-Type and Mutated RET Proto-Oncogene Associated with Familial Medullary Thyroid Cancer

“…In Portugal and Czech Republic, the most common mutation was codon 918 for the sporadic form of MTC (Zedenius et al, 1994). In USA the most common mutation in this gene was at codon 634 in patients with hereditary MTC (Moura et al, 2009). In Iran and China also the highest genetic variation and mutation was reported at codon 634 (Zhou et al, 2007;Hedayati et al, 2011).…”