Endocrine Abstracts

Background: Medullary thyroid carcinoma (MTC) is a rare calcitonin producing neuroendocrine tumour that originates from parafollicular C-cells of the thyroid gland. RET proto-oncogene germline mutations are crucial for the onset and the progression of MTC, and the occurrence of single nucleotide polymorphisms could predispose the clinical course of disease. The objective of this study was to evaluate possible differences in clinical presentation among patients with/without RET codon 790 and codon 791 (exon 13) mutations.

Methods: A non-isotopic polymerase chain reaction based single strand confirmation polymorphism analysis and heteroduplex gel electrophoresis method was used to screen tumour DNA extracted from 132 formaldehyde fixed and paraffin embedded MTC specimens. We analysed clinical data from 69 patients harbouring RET codon 790 and codon 791 mutations (exon 13) (group A) compared with 63 patients with “wild-type” genotype (group B). The study was conducted according to the Declaration of Helsinki, the protocol was reviewed and approved by the institutional independent ethics committee. All patients were provided with written informed consent.

Results: Mean age for the group A was 56.2±11.4 years (range, 44.8–67.6) vrs. 49.4±9.7 (range 39.7–59.1) for the group B. Lymph node metastases were found in all patients (group A, n=46 vrs. group B, n=31; P<0.001), and distant metastases in 11 patients (group A, n=7 vrs. group B, n=4; P>0.001). Postoperatively, 62% of patients in group A vrs. 78% of patients in group B were biochemically cure (P<0.001). In the group A, pT-category was: T₀, n=21; T₁, n=16; and T₂, n=9. In the group B, pT-category was: T₀, n=22; T₁, n=7; and T₂, n=2 (P<0.001).

Conclusions: Patients with RET codon 790/791 (exon13) mutations have a more aggressive clinical course and lower biochemic cure rate in comparison with patients with ‘wild-type’ genotype. This information should be considered by genetic counseling or by operative therapy and could have clinical importance when specific targeted therapy is discussed.