title: Prognostic significance of serine 392 phosphorylation in overexpressed p53 protein in human esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  Posttranscriptional modification involving phosphorylation of wild-type p53 has been considered to play a role in the stabilization of p53. Little is known, however, about the role of phosphorylation of mutant p53 overexpressed in tumors. The aim of this study is to determine the phosphorylation state of p53 in tumors and its contribution to tumor development.
  
  
  METHODS
  Using immunohistochemical techniques, we examined the phosphorylation of Ser392 and 15 sites in p53 overexpressed in 137 esophageal squamous cell carcinomas (ESCCs). The relationships between the phosphorylation and the expression of cell cycle regulators, Ki-67 labeling index (LI), apoptotic index, clinicopathological factors, and patient prognosis were tested statistically.
  
  
  RESULTS
  Of the 137 samples examined, staining for Ser392 phosphospecific p53 antibody was detected in 53 (38.7%) cases, corresponding to 58.9% of 90 p53-positive cases, whereas only 3 (2.2%) were positive for Ser15 phosphospecific p53 antibody. A significant correlation was identified between Ser392 phosphorylation and high levels of Ki-67 LI (p = 0.0271), lymphatic invasion (p = 0.0246), and poorer prognosis for patients with stage II and III advanced tumors (p = 0.0136). Using multivariate analysis, Ser392 phosphorylation was recognized as an independent prognostic factor (p = 0.0136).
  
  
  CONCLUSIONS
  These findings suggest that p53 protein overexpressed in ESCCs is frequently phosphorylated at Ser392, and that the Ser392 phosphorylation might contribute to tumor progression of ESCCs.
authors.affiliation: Department of Tumor Pathology, Kochi University, Nankoku, Kochi, Japan. manabu@med.kochi-u.ac.jp
authors.forename: Manabu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurabayashi
authors.forename: Siro
authors.initials: S
authors.lastname: Sasaguri
authors.forename: Keijiro
authors.initials: K
authors.lastname: Araki
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ohtsuki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012694:Serine / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D012694:Serine