title: Evaluation of proliferation potential in thyroid normo-/hypofunctioning and hyperfunctioning nodules.
abstract: BACKGROUND
  Thyroid follicular adenomas (FA) and adenomatous thyroid nodules (AN) - lesions that are frequently found in areas with iodine deficiency, can be normo-/hypofunctioning (scintigraphically cold - SCN) or hyperfunctioning (scintigraphically hot - SHN) nodules.
  
  
  OBJECTIVE
  Evaluation of proliferation potential in thyroid nodules on tissue samples obtained at surgery from euthyroid patients clinically diagnosed with SCN and from patients with thyroid hyperfunction and SHN.
  
  
  METHODS
  We investigated the proliferation activity estimated by assessing PCNA and Ki-67 proliferation markers in 20 SCN (eight FA and 12 AN) and 16 toxic nodules (six hyperfunctioning FA and 10 toxic multinodular goiters), on formalin-fixed and paraffin-embedded tissue samples, 4-5 μm thick; we used the immunohistochemical technique in LSAB system (DAB visualization) with anti-PCNA (PC10) and anti-Ki-67 (MIB-1) monoclonal antibodies. For each case, we calculated the proliferation index PI-PCNA and PI-Ki-67. The dates were statistically evaluated using the t-unpaired test.
  
  
  RESULTS
  We observed a higher PI-PCNA in thyroid nodules than in the normal surrounding thyroid tissue, with statistically significant values for FA (14.3% vs. 3.8%; p<0.029) and also for AN (8.36% vs. 1.24%; p<0.001). The mean PI-Ki-67 in nodules vs. surrounding thyroid tissue was 1.64% vs. 1.10% in FA (p<0.35) and 1.07% vs. 0.51% in AN (p>0.05). We also noted: (1) significantly higher PI-PCNA values (p < 0.01) in FA (14.03%) than in AN (8.36%), as compared to statistically insignificant values for Ki-67 (1.64% vs. 1.07%; p>0.05); (2) increased proliferation rate (p<0.01) in thyroid nodules with aspects of lymphocytic thyroiditis (LT) (PI-Ki-67 was 1.21%) as compared to nodules without LT (PI-Ki-67 was 0.12%); (3) a mean PI-PCNA of 8.5% and PI-Ki-67 of 4.61% in toxic thyroid nodules (TTN) vs. 3.01% and 1.5% in normal surrounding thyroid, respectively.
  
  
  CONCLUSIONS
  The clinical expression of SCN is the consequence of increased thyrocyte proliferation in the nodules; the increased proliferative potential of TTN thyrocytes is a common feature of nodules, independent of their histopathological characteristics.
authors.affiliation: Department of Pathology, Victor BabesUniversity of Medicine and Pharmacy, Timisoara, Romania. marioaracornianu@yahoo.com
authors.forename: Marioara
authors.initials: M
authors.lastname: Cornianu
authors.forename: V
authors.initials: V
authors.lastname: Stan
authors.forename: Elena
authors.initials: E
authors.lastname: Lazăr
authors.forename: Alis
authors.initials: A
authors.lastname: Dema
authors.forename: Ioana
authors.initials: I
authors.lastname: Golu
authors.forename: Sorina
authors.initials: S
authors.lastname: Tăban
authors.forename: Mihaela
authors.initials: M
authors.lastname: Vlad
authors.forename: Alexandra
authors.initials: A
authors.lastname: Faur
authors.forename: F
authors.initials: F
authors.lastname: Vărcuş
authors.forename: F
authors.initials: F
authors.lastname: Babău
mesh_terms: D000236:Adenoma / Q000473:pathology; D049109:Cell Proliferation; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D016606:Thyroid Nodule / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D013966:Thyroiditis / Q000378:metabolism / Q000473:pathology
chemical_list: D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen