OR22 HLA-G regulatory and coding region haplotypes in papillary thyroid carcinoma

Aim To evaluate HLA-G coding and regulatory (promoter and 3’ untranslated region-3’UTR) haplotypes in papillary thyroid carcinoma (PTC) patients and their associations with clinical and histopathological features. Methods We studied 185 PTC patients and polymorphic sites distributed along the three different HLA-G gene regions were characterized by Sanger sequencing. HLA-G haplotype associations were analyzed using the Fisher exact test, calculating odds ratio (OR), confidence interval (CI) and P -values. Results More than 90 variation sites were observed along the whole gene. Considering the promoter region , i) 010101d haplotype was less frequent in patients presenting classical histological variant of PTC (OR = 0.2789, CI 95% = 0.0755–1.0304, P  = 0.0499), ii) 0104a haplotype was less frequent in patients presenting tumor multicentricity (OR = 0.3360, CI 95% = 0.1446–0.7810, P  = 0.0089), and iii) 0103a haplotype was more frequent in patients presenting advanced stage of PTC at diagnosis (TNM staging III and IV) (OR = 0.3541, CI 95% = 0.1360–0.9219, P  = 0.0370). Regarding the coding region , the G *01:01:12 (+324 G ) allele was associated with the presence of tumor multicentricity (OR = 11.2857, CI 95% = 1.3438–94.7784, P  = 0.0094) and Hashimoto’s thyroiditis (OR = 6.4851, CI 95%=1.2383–33.9649, P  = 0.0224). At 3’UTR , the UTR-02 haplotype was overrepresented (OR = 1.6759, CI 95% = 1.0616–2.6456, P  = 0.0328) and UTR-03 haplotype was underrepresented (OR = 0.4106, CI 95% = 0.1912–0.8815, P  = 0.0200) in patients presenting tumor multicentricity. No association regarding tumor size, local invasion, metastasis at diagnosis and extrathyroidal extension was observed. Conclusions Although HLA-G is expressed in more than 80% of PTC specimens, HLA-G alleles were primarily associated with tumor morbidity, indicating that local factors may transcriptional and posttranscriptionally modulate HLA-G expression.