Endocrine Abstracts

The genetic instability, i.e. loss of heterozygosity (LOH) and microsatellite instability (MSI) are frequent molecular events in thyroid tumour aetiopathogenesis. They were found in several chromosomal critical areas, including 3p12–p21.2, 3p24.2–p25.3, 7q21.1–q31.2, 10q22–24, and 15q11–q13, with loci of oncogenes and tumour suppressor genes.

Aim of the study: Evaluation of usefulness of LOH/MSI as diagnostic/prognostic biomarker in follicular cell-derived thyroid tumours.

Materials: Thyroid tumour and macroscopically unchanged tissues (control) obtained from 93 patients with: follicular adenoma (FA; n=11), papillary thyroid carcinoma (PTC; n=31), follicular thyroid carcinoma (FTC; n=8), and nodular goitres (NG; n=43).

Methods: Ten microsatellite markers linked with regions 1p31.2, 3p21.3, 3p24.2, 9p21.3, 11p15.5, and 16q22.1 were amplified in PCRs and then allelotyped. Fractional allelic loss (FAL) values defined as LOH/MSI coincidence in various chromosomal regions were assessed.

Results: LOH/MSI frequency was the highest in 3p21.3–3p24.2 (15%) and 11p15.5 (14.29%), followed by 1p31.2, 9p21.3 (12%), and 16q22.1 (10.23%). Statistical analysis of LOH/MSI frequency in FTC revealed significantly increased LOH/MSI in 1p31.2 (P=0.028). Significantly increased LOH/MSI in 3p21.3 was found for pT1 tumours, AJCC stage I and tumours with diameter <10 mm; in 1p31.2: for pT2–T4, stages II–IV, and tumours with diameter 10–30 mm; in 11p15.5: for pT2–T4, stages II–IV, and tumours with diameter >30 mm (P<0.05). Mean FAL values were significantly higher in men (P=0.002), and in younger patients (<40 years, P=0.016). FAL was significantly higher in: FA and FTC compared with NG and PTC (P=0.033); pT2–T4 vs pT1 (P=0.021). Increased FAL value significantly correlated with increased tumour diameter (P=0.044).

Conclusions: Our findings confirmed LOH/MSI occurrence in 3p21.3 at early stage of tumorigenesis while in 1p31.2 and 11p15.5, not recognised as critical areas, seems to be characteristic for advanced stage of thyroid tumours. FAL defined as LOH/MSI coincidence in various chromosomal regions may be useful biomarker in prediction of tumour progression. The increased FAL values in FA/FTC can be regarded as promising distinguishing biomarker from PTC and NG.

Disclosure: This work was financially supported by the Polish Ministry of Science and Higher Education (Iuventus Plus programme, 2012–2015, grant number 0082/IP1/2011/71).