Prognostic significance of serine 392 phosphorylation in overexpressed p53 protein in human esophageal squamous cell carcinoma.
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.
Matsumoto
Manabu
M
Department of Tumor Pathology, Kochi University, Nankoku, Kochi, Japan. manabu@med.kochi-u.ac.jp
Furihata
Mutsuo
M
Kurabayashi
Atsushi
A
Sasaguri
Siro
S
Araki
Keijiro
K
Hayashi
Hideki
H
Ohtsuki
Yuji
Y
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
D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D012694:Serine