Phosphorylated AKT1 is associated with poor prognosis in esophageal squamous cell carcinoma.
BACKGROUND
The epidermal growth factor receptor (EGFR) signaling pathway is important in regulating biological behaviors in many malignancies. We explored whether expression and activation of EGFR and several components on its downstream pathways have prognostic significance in patients with esophageal squamous cell carcinoma (ESCC).


METHODS
Expression of EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3 was assessed by immunohistochemical analysis of tissue microarrays for 275 ESCC patients who had undergone complete three-field lymphadenectomy. Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS).


RESULTS
p-EGFR expression was correlated statistically with all of the other phosphorylated markers. Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS. Increased expression of p-AKT1 was associated with decreased patient survival. EGFR and p-EGFR expression was not significantly associated with patient survival.


CONCLUSIONS
Activation of AKT1 was associated with poor prognosis in ESCC.
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China. zfeizhu@aliyun.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. zfeizhu@aliyun.com.
Zhengfei
Z
Zhu
Department of Radiation Oncology, Six Hospital of Jiao Tong University, Shanghai, China. yww333@126.com.
Weiwei
W
Yu
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China. xlfu1964@hotmail.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. xlfu1964@hotmail.com.
Xiaolong
X
Fu
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. sunmh@shca.org.cn.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. sunmh@shca.org.cn.
Menghong
M
Sun
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. 10211230013@fudan.edu.cn.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. 10211230013@fudan.edu.cn.
Qiao
Q
Wei
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. lidalipopeye@gmail.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. lidalipopeye@gmail.com.
Dali
D
Li
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. hqchen1@yahoo.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. hqchen1@yahoo.com.
Haiquan
H
Chen
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. j.q.xiang@hotmail.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. j.q.xiang@hotmail.com.
Jiaqing
J
Xiang
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. lihecheng2000@hotmail.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. lihecheng2000@hotmail.com.
Hecheng
H
Li
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. zhangyawei68@hotmail.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. zhangyawei68@hotmail.com.
Yawei
Y
Zhang
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China. zwx19@126.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. zwx19@126.com.
Weixin
W
Zhao
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China. kuaile_z@sina.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. kuaile_z@sina.com.
Kuaile
K
Zhao
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000401:mortality; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018307:Neoplasms, Squamous Cell / Q000201:enzymology* / Q000401:mortality; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism
D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases