Soluble human leukocyte antigen-g and its insertion/deletion polymorphism in papillary thyroid carcinoma: novel potential biomarkers of disease?

Abstract

INTRODUCTION:

Human leukocyte antigen-G (HLA-G), a nonclassical major histocompatibility complex class I antigen, plays a pivotal role in immune tolerance and a paradoxical role in cancers.

AIMS:

Our aims were to evaluate plasma soluble HLA-G (sHLA-G) concentrations and the 14-bp insertion/deletion polymorphism of the HLA-G gene in patients with papillary thyroid carcinoma (PTC) or Hashimoto's thyroiditis (HT) and to assess the possible association of these parameters with PTC aggressiveness.

METHODS:

Samples for the analysis of sHLA-G and +14/-14-bp HLA-G polymorphism were obtained from 121 patients with HT and 183 with PTC; 245 gender- and age-matched healthy subjects served as controls. PTC histopathological aggressiveness was defined according to the last American Thyroid Association guidelines.

RESULTS:

Positive serum antithyroid antibody titers were observed in 22% of PTC patients and lymphocyte infiltration of thyroid parenchyma at histological examination in 21%, whereas both circulating and histological autoimmunity was detectable in 12% of PTC patients. No differences in the +14/-14-bp polymorphism frequencies were observed between the study groups. The prevalence of detectable sHLA-G was lower in healthy controls (52%) as compared with both HT (57%) and PTC (62%) patients. By stratifying the study groups according to sHLA-G level of positive subjects, significantly higher plasma sHLA-G values in PTC (42.9 ± 3.3 ng/ml; P = 0.002) and HT patients (49.1 ± 2.6 ng/ml; P < 0.002) as compared with healthy controls (8.5 ± 1.8 ng/ml) were obtained. Moreover, PTC patients with detectable plasma sHLA-G levels showed a higher aggressive behavior (P < 0.04) than those without.

CONCLUSIONS:

Although confirming the frequent association between PTC and chronic autoimmune thyroiditis, these data suggest that elevated circulating sHLA-G levels, besides an important signal of alterations of immune homeostasis, may be considered a potential, novel marker of PTC histopathological aggressiveness at diagnosis. Additional studies are needed to confirm the actual role and clinical relevance of the HLA-G complex in PTC development and progression.

• Authors: A Dardano, R Rizzo, A Polini, M Stignani, S Tognini, G Pasqualetti, S Ursino, C Colato, M Ferdeghini, O R Baricordi, F Monzani
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 97 Issue 11 Pg. 4080-6 (Nov 2012) ISSN: 1945-7197 [Electronic] United States
• PMID: 22930786 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• HLA-G Antigens

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• Carcinoma, Papillary (blood, genetics, pathology)
• Child
• Female
• HLA-G Antigens (blood, genetics)
• Humans
• INDEL Mutation
• Male
• Middle Aged
• Polymorphism, Genetic
• Thyroid Neoplasms (blood, genetics, pathology)
• Thyroiditis, Autoimmune (blood, genetics, pathology)