Endocrine Abstracts

Genetic instability, i.e. loss of heterozygosity (LOH) and microsatellite instability (MSI) represent molecular disorders acquired by the cell during neoplastic transformation. Genetic instability is a frequent molecular event in thyroid pathogenesis, found at the early and the late stages of thyroid tumorigenesis. In thyroid neoplasms genetic instability was found in many chromosomal regions and is observed especially in cell-derived thyroid tumours. Alterations in PTEN loci were previously detected in hereditary form of follicular thyroid cancer. In this study we focused on to the following chromosomal regions: 10q23.2, 10q.23.31, 10q24–24.1 – the loci of MMRN2, KIF11, PAPSS2 and PTEN genes.

Aim of the study: An attempt to answer the question whether the presence of LOH/MSI in 10q in thyroid carcinomas can be regarded as diagnostic marker.

To analyze the potential role of LOH/MSI in 10q involved in follicular cell-derived thyroid pathogenesis – were performed PCRs using four microsatellite markers (D10S1687, D10S583, D10S215, D10S541). The study included a group of 93 patients with initial diagnosis of ‘follicular neoplasm’ in FNAB, afterwards verified as benign (FA), malignant thyroid lesions (PTC, FTC) or nodular goitres (NG).

The LOH/MSI analysis was conducted using allelotyping method on 3130 xl Genetic Analyzer (Applied Biosystems, Hitachi) and the allele detection was assessed using GeneMapper Software v 4.0.

The highest genetic instability was detected in PAPSS2 locus (10q24; D10S215 marker) – with the frequency – 22%, and the lowest in KIF11 locus (10q24.1; D10S583). LOH/MSI was detected for any of four markers in 26 from 93 patients (28%), with the higher frequency for FTC and FA group. In FTC group, the most frequent genetic instability (LOH/MSI) was observed for D10S215 in PAPSS2 locus, in FA group for D10S541 in PTEN locus. In PTC specimens LOH/MSI was detected mainly for D10S1687 marker in MMRN2 locus.

The obtained data confirmed the presence of LOH/MSI in 10q in the early and late stage of thyroid cancerogenesis. The different frequency of LOH/MSI occurrence in analysed loci may be considered as potential marker differentiating the PTC from FA and FTC.