title: Markers of cell proliferation, apoptosis, and angiogenesis in thyroid adenomas: a comparative immunohistochemical and genetic investigation of functioning and nonfunctioning nodules.
abstract: OBJECTIVE
  To perform (i) an immunohistochemical investigation of cell proliferation, apoptosis, angiogenesis, and malignancy markers in 15 functioning and 15 nonfunctioning thyroid adenomas, and in normal adjacent tissue, and (ii) a genetic analysis of thyroid-stimulating hormone receptor (TSH-r), Gsalpha, and RAS mutations in the same group of adenomas, in order to describe their expression within tissues and to correlate them with the hormonal functioning.
  
  
  METHODS
  Thirty patients who underwent surgery for a solitary thyroid nodule were included in the study. Adenomas and normal adjacent tissues were evaluated by immunohistochemistry using the following antibodies: MIB-1 for proliferative activity, bcl-2 and mutant p53 for apoptosis control, vascular endothelial growth factor-A (VEGF-A) for angiogenic activity, and galectin-3 as a marker for malignancy. To calculate microvascular density, "hot spots" were selected and defined by cells positive for CD34 staining. Genetic analysis for TSH-r, Gsalpha, and H-, K-, and N-RAS mutations was performed on adenoma specimens.
  
  
  RESULTS
  Our results evidenced that a proportion of both functioning and nonfunctioning adenomas showed immunohistochemical phenotypes similar to normal adjacent tissue. No differences were found between functioning and nonfunctioning thyroid adenomas with regard to the expression of markers associated to angiogenesis (VEGF-A, microvascular density) and apoptosis control (mutant p53, bcl-2). All adenomas resulted negative for galectin-3 immunostaining. MIB-1 was the only marker showing a substantial difference of expression between the two groups of adenomas. TSH-r mutations were found in 12 out of 15 functioning adenomas, whereas the absence of Gsalpha and H-, K-, and N-RAS mutations was demonstrated in all adenomas.
  
  
  CONCLUSIONS
  Our data suggest that the differences between functioning and nonfunctioning thyroid adenomas are restricted to the genetic mutations of the TSH-r, to the hormonal status of tumors, and to the proliferative activity, not involving markers of apoptosis control and angiogenesis.
authors: Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, University of Pisa, Pisa, Italy. p.viacava@med.unipi.it
authors: Paolo
authors: P
authors: Viacava
authors: Guido
authors: G
authors: Bocci
authors: Massimo
authors: M
authors: Tonacchera
authors: Giovanni
authors: G
authors: Fanelli
authors: Melissa
authors: M
authors: DeServi
authors: Patrizia
authors: P
authors: Agretti
authors: Edoardo
authors: E
authors: Berti
authors: Orlando
authors: O
authors: Goletti
authors: Paolo
authors: P
authors: Aretini
authors: Maria Letizia
authors: ML
authors: Resta
authors: Generoso
authors: G
authors: Bevilacqua
authors: Antonio Giuseppe
authors: AG
authors: Naccarato
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018952:Antigens, CD34 / Q000096:biosynthesis; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009389:Neovascularization, Pathologic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53