20P - Distinctive genomic profile of lymph node profile and distant metastasis in papillary thyroid cancer

Background

Thyroid carcinoma (TC) is the most common cancer in the endocrine system. Despite papillary thyroid cancer (PTC) having a good prognosis, some thyroid tumours with aggressive behaviour develop metastases. The molecular mechanisms underlying TC metastases are poorly understood. Lymph node (LNM) or distant metastases (DM) presence has a different meaning in the prognosis of the disease, being the DMs the most frequent cause of death. The discovery of distinctive genomic biomarkers will improve the diagnosis and treatment of TC, anticipating the development of DMs.

Methods

By analysing 41 PTCs with LNM or DM we sought to determine the prevalence of mutations in genes associated with carcinogenesis, progression, and aggressiveness in TC (BRAF, RAS, TERTp, and PIK3CA). To assess the prevalence, clonal nature, and implication in dedifferentiation at least one area of the primary tumour and matched metastases were studied in 39 cases. Genotyping was approached by PCR and direct sequencing.

Results

Of 41 cases analyzed 30 were altered (73%). The prevalences of mutations in PTCs-DM were 55% BRAF, 45% RAS, 10% PIK3CA, and 55% TERTp, and for PTCs-LNM 52% BRAF, 5% RAS, 5% PIK3CA, and 33% TERTp. No significant associations were found among the genes. The coexistence of mutations among both cohorts also differed, 46% of the cases showed at least two alterations in PTCs-LNM and 65% for PTCs-DM. When the 41 cases were analyzed, RAS reported an association with the DM presence (p=0.004), BRAF with the recurrence (p=0.030), and PIK3CA correlated with patients age ≥ 55 years old. TERTp mutations displayed associations with the patient status (DOD, p=0.008) and mortality (p=0.041).

Conclusions

PTC-LNMs and PTC-DMs can be distinguished by genomic biomarkers. Despite BRAF alterations having a similar prevalence in both cohorts, RAS revealed a strikingly higher percentage of mutations in PTC-DMs compared to PTC-LNMs. Genomic alterations presented several associations with clinic-pathological characteristics that will help to improve the management of TC. The high number of cases with mutations coexisting in the ones with DMs is congruent with the hypothesis that tumour progression and aggressiveness rely on the progressive accumulation of genetic alterations.

Clinical trial identification

Legal entity responsible for the study

University of Valladolid.

Funding

Valladolid University SACYL.

Disclosure

All authors have declared no conflicts of interest.