Expression of phosphorylated Akt (pAkt) in gastric carcinoma predicts prognosis and efficacy of chemotherapy.
BACKGROUND
The Akt signaling pathway controls the survival and growth of human cancers. We investigated the expression of phosphorylated Akt (pAkt) in patients with gastric cancer.


METHODS
The expression of pAkt was immunohistochemically examined in 140 gastric cancer patients who underwent a gastrectomy. The expression of pAkt was evaluated based on staining intensity, and staining was classified as negative or positive. We examined the expression of pAkt and its association with the clinicopathological findings, prognosis, depth of invasion, the expression of p53, and efficacy of oral fluorouracil chemotherapy after surgery.


RESULTS
Expression of pAkt was positive in 81 (58%) patients and negative in 59 (42%) patients. There were no significant correlations between pAkt expression and the clinicopathological findings. The prognosis of patients with pAkt-negative tumors was superior to that of patients with pAkt-positive tumors, and the difference was significant for T3/T4 gastric cancer (P < 0.05). Among the patients with T3/T4 gastric cancer, postoperative oral fluorouracil treatment was effective in those who were pAkt-positive. Multivariate analysis revealed that pAkt expression and lymph node metastasis were independent prognostic factors. In 88 patients with T3 gastric carcinoma who had undergone curative surgery, in whom we studied the prognostic impact of a combined analysis of pAkt and p53 expression, patients with both pAkt- and p53-positive tumors showed a significantly poorer prognosis than patients with either or both pAkt- and p53-negative tumors (P < 0.05).


CONCLUSIONS
Our results indicate that pAkt expression may be useful for predicting the prognosis and efficacy of fluorouracil treatment in patients with gastric cancer.
Murakami
Daiki
D
Department of Surgery, Division of Surgical Oncology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
Tsujitani
Shunichi
S
Osaki
Tomohiro
T
Saito
Hiroaki
H
Katano
Kuniyuki
K
Tatebe
Shigeru
S
Ikeguchi
Masahide
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D016019:Survival Analysis; D005641:Tegafur / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D000964:Antimetabolites, Antineoplastic; D016159:Tumor Suppressor Protein p53; D005641:Tegafur; D051057:Proto-Oncogene Proteins c-akt; D005472:Fluorouracil