Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients

Modigliani, E; Cohen, R.; Campos, José‐Marie; Conte-Devolx, B.; Maes, Béatrice; Boneu, A; Schlumberger, Martin; Bigorgne, J. C.; Dumontier, Philippe; Leclerc, L; Corcuff, B; Guilhem, Isabelle

doi:10.1046/j.1365-2265.1998.00392.x

Cited by 510 publications

(484 citation statements)

References 26 publications

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“…Although clinical and pathological variables alone may suffice to predict patient outcome in most cases, the variable behavior of MTC in some cases suggests that, in the same clinical and pathological conditions, cancer progression and survival may also be influenced by other biological elements (5,6).…”

Section: Introductionmentioning

confidence: 99%

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

Mian

Pennelli²,

Barollo

et al. 2011

European Journal of Endocrinology

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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

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Section: Introductionmentioning

confidence: 99%

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

Mian

Pennelli²,

Barollo

et al. 2011

European Journal of Endocrinology

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“…Ten-year survival rates for patients with stages I, II, III and IV MTCs are 100%, 93%, 71% and 21%, respectively (Modigliani et al 1998). In the last decades, there has been no significant trend towards an earlier stage of disease at the time of diagnosis.…”

Section: :1mentioning

confidence: 99%

Animal models of medullary thyroid cancer: state of the art and view to the future

Mantovani

Gaudenzi

Circelli

et al. 2017

Endocrine-Related Cancer

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Medullary thyroid carcinoma is a neuroendocrine tumour originating from parafollicular C cells accounting for 5-10% of thyroid cancers. Increased understanding of diseasespecific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid carcinoma. These drugs increase progression-free survival; however, they are often poorly tolerated and most treatment responses are transient. Animal models are indispensable tools for investigating the pathogenesis, mechanisms for tumour invasion and metastasis and new therapeutic approaches for cancer. Unfortunately, only few models are available for medullary thyroid carcinoma. This review provides an overview of the state of the art of animal models in medullary thyroid carcinoma and highlights future developments in this field, with the aim of addressing salient features and clinical relevance. 24:1

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“…Timely thyroidectomy in family members carrying an inherited mutated RET allele prevents MTC, the most common cause of death in MEN2 syndromes (Modigliani et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of the MTC-associated germline RET-K666E mutation: evidence of oncogenic potential enhanced by the G691S polymorphism

Borrello¹,

Aiello²,

Peissel³

et al. 2011

Endocrine-Related Cancer

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Activating mutations of RET, a gene encoding two isoforms of a tyrosine kinase receptor physiologically expressed in several neural crest-derived cell lineages, are associated with the inherited forms of medullary thyroid carcinoma (MTC). The identification and characterization of novel RET mutations involved in MTC is valuable, as RET gene testing plays a crucial role in the management of these patients. In an MTC patient, we have identified a germline c.1996AOG transition in heterozygosis leading to K666E substitution. In addition, the conservative S904S (c.2712COG) and the non-conservative functional G691S (c.2071GOA) polymorphisms have been identified. Through functional studies, we demonstrate for the first time that K666E is a gain-of-function mutation with oncogenic potential, based on its ability to transform NIH3T3 cells. It was not possible to define whether K666E is a de novo or inherited RET variant in the patient, as the family history was negative for MTC, and the carrier status of family members could not be tested. Our results, together with a recent report of co-segregation of the mutation in three MTC families, suggest that K666E is a causative MTC mutation. As we have shown that the same patient allele carries both K666E and G691S variants, the latter known to increase downstream RET signaling, a possible role for the G691S polymorphism has also been investigated. We have demonstrated that, although RET-G691S is not oncogenic per se, it enhances the transforming activity of the RET-K666E mutant, thus suggesting a modifier role for this functional polymorphism.

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Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients

Abstract: Survival of these medullary thyroid carcinoma patients appears better than expected even in non-cured patients. Considering the strong impact of stage, the necessity for pre-operative diagnosis of MTC is obvious.

Cited by 510 publications

References 26 publications

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

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

Animal models of medullary thyroid cancer: state of the art and view to the future

Functional characterization of the MTC-associated germline RET-K666E mutation: evidence of oncogenic potential enhanced by the G691S polymorphism

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