title: Soluble human leukocyte antigen-g and its insertion/deletion polymorphism in papillary thyroid carcinoma: novel potential biomarkers of disease?
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.affiliation: Geriatrics Unit, Department of Internal Medicine, University of Pisa, I-56126 Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Dardano
authors.forename: R
authors.initials: R
authors.lastname: Rizzo
authors.forename: A
authors.initials: A
authors.lastname: Polini
authors.forename: M
authors.initials: M
authors.lastname: Stignani
authors.forename: S
authors.initials: S
authors.lastname: Tognini
authors.forename: G
authors.initials: G
authors.lastname: Pasqualetti
authors.forename: S
authors.initials: S
authors.lastname: Ursino
authors.forename: C
authors.initials: C
authors.lastname: Colato
authors.forename: M
authors.initials: M
authors.lastname: Ferdeghini
authors.forename: O R
authors.initials: OR
authors.lastname: Baricordi
authors.forename: F
authors.initials: F
authors.lastname: Monzani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D059951:HLA-G Antigens / Q000097:blood / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013964:Thyroid Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000235:genetics / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D059951:HLA-G Antigens