Follicular Thyroid Adenoma and Follicular Thyroid Carcinoma-A Common or Distinct Background? Loss of Heterozygosity in Comprehensive Microarray Study

Abstract

Pre- and postsurgical differentiation between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC) represents a significant diagnostic challenge. Furthermore, it remains unclear whether they share a common or distinct background and what the mechanisms underlying follicular thyroid lesions malignancy are. The study aimed to compare FTA and FTC by the comprehensive microarray and to identify recurrent regions of loss of heterozygosity (LOH). We analyzed formalin-fixed paraffin-embedded (FFPE) samples acquired from 32 Caucasian patients diagnosed with FTA (16) and FTC (16). We used the OncoScan™ microarray assay (Affymetrix, USA), using highly multiplexed molecular inversion probes for single nucleotide polymorphism (SNP). The total number of LOH was higher in FTC compared with FTA (18 vs. 15). The most common LOH present in 21 cases, in both FTA (10 cases) and FTC (11 cases), was 16p12.1, which encompasses many cancer-related genes, such as TP53, and was followed by 3p21.31. The only LOH present exclusively in FTA patients (56% vs. 0%) was 11p11.2-p11.12. The alteration which tended to be detected more often in FTC (6 vs. 1 in FTA) was 12q24.11-q24.13 overlapping FOXN4, MYL2, PTPN11 genes. FTA and FTC may share a common genetic background, even though differentiating rearrangements may also be detected.

Keywords: follicular thyroid adenoma; follicular thyroid cancer; genetics; loss of heterozygosity; microarray; molecular inversion probe.

Figure 1

(a) The overlapping chromosomal regions with loss of heterozygosity in follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA). The first set shows LOH present only in follicular thyroid cancer, the second both in FTC and FTA, and the third shows LOH present only in FTA. Findings from the present study are in bold. Other regions (not in bold) were found in the literature [19,21,26,27,28,29,30,31,32]. (b) The most important genes included in overlapping chromosomal regions with loss of heterozygosity in follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA). * represents statistical significance at p < 0.05; # represents regions present only in FTC or in both FTC and FTA (the latter in our study).