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

Abstract

Objective: Medullary thyroid carcinoma (MTC) derives from the parafollicular C cells, being sporadic in 75% of cases and familial in 25%, due to RET proto-oncogene germinal mutations. In sporadic forms, stage at diagnosis is the most important negative prognostic factor. The aim of this study was to evaluate the prognostic impact of molecular and immunohistochemical markers in sporadic MTC. Design and methods: We studied 60 patients with sporadic MTC. For each case, we sought RET somatic mutations in the primary cancer and in lymph node metastases. The primary cancer also underwent immunohistochemical examination for Ki-67. Results: A somatic RET mutation was found in 38% of patients, being M918T in 52% of them. We observed a statistically significant association between RET mutations and male gender (P!0.01), tumor size (P!0.05), lymph nodes (P!0.05) and distant metastases (P!0.001), advanced stage (P!0.05), increased risk of persistent disease (PZ0.01), and low overall survival (P!0.01). High Ki-67 levels were similarly associated with extra-thyroid spread (P!0.05), lymph nodes (P!0.05) and distant metastases (P!0.001), advanced stage (PZ0.01), and low overall survival (PZ0.01). Combining somatic RET analysis with Ki-67 assessment seems to be useful for increasing the specificity of Ki-67 assessment alone and identifying patients with a more aggressive cancer: in our series, only the patients who died during the follow-up had both a somatic RET mutation and a Ki-67 expression level O50 cells/mm 2 . Conclusions: The combined evaluation of RET and Ki-67 could act as an adjuvant prognostic marker useful for ameliorating the initial risk stratification of patients with sporadic MTC.European Journal of Endocrinology 164 971-976

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).…”

Częstość występowania mutacji somatycznych RAS w raku rdzeniastym tarczycy — analiza populacji polskiej

“…The prevalence of RET somatic mutations (57,8%) in our analysed group is consistent with previous reports [15,[29][30][31], where the frequency of somatic RET mutation ranges between 38% [29] and 71% [15]. Moreover, similarly to other data [29,30], the most frequent somatic RET mutation in our group was M918T, which constituted nearly 50% of all RET somatic mutations.…”

ENDOCRINE TUMOURS: Progressive metastatic medullary thyroid carcinoma: first- and second-line strategies

“…Mutation analysis " Mutations in the RET oncogene are found in the familial forms of MTC and in more than 45% of sporadic MTC (26,27,28 (29). The most common and more aggressive somatic RET mutation in sporadic MTC is the replacement of methionine by threonine at codon 918 (Met918Thr), although mutations and deletions have been described at a number of other codons.…”