The activation of Akt during preoperative chemotherapy for esophageal cancer correlates with poor prognosis.
The activation of the PI3K/Akt/mTOR pathway plays an important role in tumorigenesis and resistance to anticancer drugs. The aim of this study was to elucidate the role of the Akt/mTOR pathway in chemoresistance and the prognosis of patients with esophageal squamous cell carcinoma (ESCC) who received preoperative chemotherapy. We evaluated p-Akt and p-mTOR expression by immunohistochemistry in the surgical specimens of 143 ESCC (51 patients with and 92 without preoperative chemotherapy). In 37 patients of the former group, paired tissue samples obtained before and after chemotherapy were examined immunohistochemically. The incidence of p-Akt expression was higher in ESCC with than without chemotherapy (51.0 vs. 25.0%, p=0.0018). Although p-Akt expression was not associated with an advanced tumor stage, a comparison between before and after chemotherapy demonstrated an increased p-Akt expression during chemotherapy (p=0.0348). The p-Akt expression did not correlate with survival in ESCC without chemotherapy, but was associated with poor prognosis in those with chemotherapy (p=0.0058). In particular, an increased p-Akt expression during chemotherapy was associated with poor survival (p=0.0022). Notably, the p-mTOR expression did not correlate with p-Akt expression (p=0.1482). The depth of the tumor invasion, clinical response and p-Akt expression correlated with the prognosis of 51 ESCC with chemotherapy. A multivariate analysis showed that p-Akt expression was the only independent predictor of poor prognosis in ESCC patients with chemotherapy. p-Akt expression increases after chemotherapy in ESCC and a high expression correlates with poor prognosis. Our results suggest that the activation of Akt is a potentially useful therapeutic target in ESCC patients treated with chemotherapy.
Yoshioka
Akiko
A
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Miyata
Hiroshi
H
Doki
Yuichiro
Y
Yasuda
Takushi
T
Yamasaki
Makoto
M
Motoori
Masaaki
M
Okada
Kazuyuki
K
Matsuyama
Jin
J
Makari
Youichi
Y
Sohma
Itsuro
I
Takiguchi
Shuji
S
Fujiwara
Yoshiyuki
Y
Monden
Morito
M
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology* / Q000601:surgery*; D003131:Combined Modality Therapy / Q000379:methods; D004789:Enzyme Activation; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000601:surgery*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011494:Protein Kinases / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases