title: Immunoreactions for P53 isoforms are associated with ultrastructural proliferative profiles in benign thyroid nodules.
abstract: BACKGROUND
  P53 isoforms originate from the alternative initiation of P53 gene translation through usage of an internal promoter located in intron 4. All P53 isoforms are spliced in intron 9 and may modulate cell proliferation and cell fate outcome in response to DNA damage.
  
  
  OBJECTIVE
  To examine immunoexpression of P53 isoforms in benign proliferative lesions occurring in multinodular thyroids and to assess the ultrastructural phenotype of P53 distribution in the thyrocytes of those lesions by electron microscopy.
  
  
  METHODS
  By immunohistochemistry and transmission electron microscopy (TEM), we evaluated 38 multinodular thyroids containing a total of 102 benign lesions: 38 nodular goiters (NG; colloid=20, parenchymatous=18), 52 follicular adenomas (FA) and 12 Hashimoto's thyroditis (HT). FA were classified into 10 normo-follicular, 9 macro-follicular, 28 micro-follicular and 5 solid variants.
  
  
  RESULTS
  Immunoreaction for P53 isoforms was observed in approximately 50% of all lesions, except macrofollicular variant FA (33%). At TEM analysis, immunoreactive NG, FA and TH lesions showed signs of proliferation by simultaneous appearance of dispersed chromatin, increased amounts of cytoplasmic organelles and dilation of the rough endoplasmic reticulum. TEM signs of apoptosis and proliferation were also detected in FA, but with different rates compared to NG.
  
  
  CONCLUSIONS
  The immunohistochemical expression of P53 isoforms in NG, FA and HT suggests their role in the development of these lesions. Ultrastructural findings support the hypothesis that P53 immunoexpression correlates with reactive proliferative changes in thyrocytes.
authors.affiliation: Department of Clinical and Experimental Medicine and Department of Human Pathology of the adult and development, University of Messina, Messina, Italy. mariatrovato@tin.it.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Trovato
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. rmruggeri@unime.it.
authors.forename: Rosaria Maddalena
authors.initials: RM
authors.lastname: Ruggeri
authors.affiliation: Department of Human Pathology of the adult and development, University of Messina, Messina, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Scardigno
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Sturniolo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vita
authors.affiliation: Department of Human Pathology of the adult and development, University of Messina, Messina, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Vitarelli
authors.affiliation: Department of Human Pathology of the adult and development, University of Messina, Messina, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Arena
authors.affiliation: Department of Human Pathology of the adult and development, University of Messina, Messina, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Gambadoro
authors.affiliation: Department of Human Pathology of the adult and development, University of Messina, Messina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sturniolo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Trimarchi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Benvenga
authors.affiliation: Division of Cancer Research Jacqui Wood Cancer Centre, University of Dundee, Dundee, UK.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Bourdon
authors.affiliation: Department of Human Pathology of the adult and development, University of Messina, Messina, Italy and Interdepartmental program of Ultrastructural Integrated Diagnostic, AOU "G. Martino", Messina, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Cavallari
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D020033:Protein Isoforms / Q000378:metabolism; D016606:Thyroid Nodule / Q000473:pathology / Q000648:ultrastructure*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D020033:Protein Isoforms; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53