Endocrine Abstracts (2011) 26 OC4.4

HLA-G polymorphism and papillary thyroid cancer histological aggressiveness

A Dardano1, R Rizzo2, A Polini1, M Stignani2, S Tognini1, M Ferdeghini3, O Baricordi2 & F Monzani1


1University of Pisa, Pisa, Italy; 2University of Ferrara, Ferrara, Italy; 3University of Verona, Verona, Italy.


Introduction: Human leukocyte antigen-G (HLA-G) is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. Its main role is the maintenance of tolerance between maternal immune system and semiallogenic fetus. The expression of HLA-G antigen has been reported in several cancers and seems to play an important role in the escape of tumour cells from immune surveillance. A 14 bp insertion/deletion polymorphism in exon 8 of the 3′ untranslated region of the HLA-G gene has been reported to be associated with HLA-G mRNA stability.

Aim: To evaluate the prevalence of the 14 bp insertion (+14 bp) and deletion (−14 bp) polymorphism in the HLA-G gene in patients affected by papillary thyroid carcinoma (PTC) as well as autoimmune thyroiditis. The possible association between HLA-G 14 bp polymorphism and thyroid cancer aggressiveness was also assessed.

Patients and methods: We studied 182 patients (147 F) with PTC; 120 patients (104 F) with autoimmune thyroiditis and 245 healthy subjects (191 F), matched for sex and age, served as control groups. HLA-G polymorphism was studied by PCR techniques.

Results: The frequency of the 14 bp insertion polymorphism was significantly higher in patients with PTC and autoimmune thyroiditis as compared to healthy controls (0.48 and 0.46 vs 0.38, P=0.0003 and P=0.01, respectively). Among PTC patients, a significant correlation was found between +14 bp allele and advanced TNM stage (ρ: 0.37, P<0.0001), as well as higher tumour aggressiveness, expressed as lymph node and/or multifocality and/or thyroid capsule invasion (ρ: 0.39, P<0.0001). A positive correlation between the +14 bp allele and cancer dimension was also observed (ρ: 0.15, P<0.05).

Conclusions: Our preliminary data show, for the first time, an increased frequency of the 14 bp insertion polymorphism in PTC patients, suggesting a potential role of the HLA-G polymorphism in PTC immune escape and aggressiveness. The polymorphism may be also involved in the reported increased prevalence of PTC in patients with autoimmune thyroiditis.

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