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.

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

“…Immunohistochemical detection of phosphorylated Ser 392 is more frequent in breast cancers with mutant rather than wild-type p53 (Nenutil et al, 2005). In other tumours the presence of p53 phosphorylated at Ser 392 has been associated with poorer survival (Matsumoto et al, 2004). In this series its presence related to a shorter duration of survival, particularly for those patients receiving adjuvant hormonal therapy.…”

Expression of p53 Protein Phosphorylated at Serine 20 and Serine 392 in Malignant and Benign Ovarian Neoplasms

“…Other authors think that p53 phosphorylated at Ser392 may be considered an independent prognostic factor in advanced human esophageal squamous cell carcinomas (ESCCs). 15 To our knowledge, there are no data in the literature involving an evaluation of p53 protein phosphorylation at Ser20 and Ser392 in ovarian neoplasms.…”

“…7,13Y17 Only individual results have shown a clinical implication of p53 phosphorylation in human cancer. 15,17 Yap et al 17 suggested that p53-Ser392 phosphorylation may regulate the oncogenic function of mutant forms of p53 protein in breast cancer. Other authors think that p53 phosphorylated at Ser392 may be considered an independent prognostic factor in advanced human esophageal squamous cell carcinomas (ESCCs).…”

CyclinD1, p53, E‐cadherin, and VEGF discordant expression in paired regional metastatic lymph nodes of esophageal squamous cell carcinoma: A tissue array analysis

“…Mutated P53 protein was frequently phosphorylated at Ser392 [25]. Matsumoto et al [26] identified a significant correlation between Ser392 phosphorylation P53 and lymphatic invasion for patients with stage II and III advanced ESCC. However, the correlation between increased immunocreactivity and the presence of mutations is somewhat imperfect [27].…”