Predictive value of p53 and 14-3-3sigma for the effect of chemoradiation therapy on esophageal squamous cell carcinoma.
OBJECTIVE
The p53 family regulates cell-cycle arrest, triggers apoptosis, repairs DNA damage caused by various genotoxic stresses, and protects cells from death upon irradiation. The purpose of the present study was to examine the expressions of p53 and one of the p53 family proteins, 14-3-3sigma, in biopsy specimens and to predict the clinical and histological responses to chemoradiation therapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC).


METHODS
We investigated with the relationship between p53 and 14-3-3sigma expressions in biopsy specimens obtained from 62 patients with ESCC and analyzed these patients' clinical and histological responses to CRT. Chemoradiation therapy consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation.


RESULTS
Following CRT, 71.0% of patients showed a positive clinical response and 52.8% showed a positive histological response. The rate of positive expression was 43.5% for p53 and 58.1% for 14-3-3sigma. Statistically significant correlations were found between p53 expression and clinical response to CRT (P = 0.001) and histological response to CRT (P = 0.041), and between 14-3-3sigma expression and histological response to CRT (P = 0.01). Furthermore, in p53-positive tumors, CRT was more effective in tumors with 14-3-3sigma-positive expressions than those with 14-3-3sigma-negative expressions (P = 0.037). The survival rate of the patients with 14-3-3sigma-positive tumors was better than those with 14-3-3sigma-negative tumors in patients with p53-positive tumors (P = 0.047).


CONCLUSIONS
We demonstrated that p53-negative or 14-3-3sigma-positive expressions were closely related to the response to CRT. It is clinically useful to examine the expression of these genes in biopsy specimens for predicting the CRT outcomes in patients with ESCC.
Department of Surgical Oncology, Digestive Surgery, Graduate School of Medicine, Kagoshima University, Kagoshima, Japan. hokumura@m.kufm.kagoshima-u.ac.jp
Hiroshi
H
Okumura
Shoji
S
Natsugoe
Masataka
M
Matsumoto
Naoya
N
Yokomakura
Yasuto
Y
Uchikado
Hiroyuki
H
Takatori
Sumiya
S
Ishigami
Sonshin
S
Takao
Takashi
T
Aikou
D048948:14-3-3 Proteins; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D005092:Exonucleases / Q000096:biosynthesis*; D005095:Exoribonucleases; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011879:Radiotherapy Dosage; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D002945:Cisplatin; D005472:Fluorouracil