Endocrine Abstracts

Background: Medullary thyroid cancer (MTC) makes up to 5–10% of all cases of thyroid malignancies. The clinical course of MTC varies from an extremely indolent tumour to an aggressive variant that is associated with a high mortality rate. RET proto-oncogene germline mutations are crucial for the onset and the progression of MTC. The aim of this study was to evaluate the L769L (subgroup L) and S836S (subgroup S) allele frequencies in patients with sporadic MTC (group A, n=89) compared to healthy subjects (group B, n=83) and to determine if these polymorphisms have influence the clinical presentation and the course of MTC.

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 89 formaldehyde fixed and paraffin embedded MTC specimens. We also analysed relevant clinical data in the group of patients with MTC. 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 was 51.6±9.2 years for the patients with MTC (range, 42.4–60.8) vs 45.4±7.1 (range 38.3–52.5) for the group of healthy subjects. The allele frequencies showed a similar level of the L769L and S836S variants in both subgroups of examinees (group L, 52.5% vs group S, 47.5%; P>0.001). Lymph node metastases were found in all patients with MTC (subgroup L, n=42 vs subgroup S, n=47; P>0.001), and distant metastases in nine patients (subgroup L, n=5 vs subgroup S, n=4; P>0.001). Postoperatively, 52% of patients in subgroup L vs 55% of patients in subgroup S were biochemically cure (P>0.001). In the subgroup L, pT-category was: T0, n=23; T1, n=14; and T2, n=5. In the subgroup S, pT-category was: T0, n=21; T1, n=16; and T2, n=10.

Conclusion: We did not find any statistically significant difference in representation of the L769L and S836S gene variants. The RET L769L and S836S (exon 11, 13, 14, and 15) gene variants are not contributing factor in the development of sporadic MTC and are not promoting factor for development of metastatic MTC.