Activated Akt and Erk expression and survival after surgery in pancreatic carcinoma.
BACKGROUND
Long-term survival of surgically resectable pancreatic cancer patients is uncommon. The epidermal growth factor receptor (EGFR) and the phosphoinositol-3-kinase pathways are often activated in pancreatic cancer, and an understanding of their role in resected cases may help refine adjuvant therapy.


METHODS
We investigated the expression of EGFR, Erk, Akt, and their phosphoforms (p-) in pancreatectomy specimens and correlated these with survival. Thirty-nine consecutive surgically resected pancreatic adenocarcinoma cases were included. Immunohistochemical staining of paraffin-embedded blocks was performed by using monoclonal antibodies against EGFR, Erk, p-Erk, Akt, and p-Akt. A standard immunoperoxidase technique was used to detect the avidin-biotin peroxidase complex. Immunostaining was visually scored with the histoscore method by two surgical pathologists.


RESULTS
Patient characteristics were as follows: 17 men and 22 women; median age, 66 years; and American Joint Committee on Cancer stage I, 5 patients; stage II, 4 patients; stage III, 27 patients; and stage IV, 3 patients. The tumor was World Health Organization grade 1 in 4, grade 2 in 17, and grade 3 in 18 cases. Adjuvant therapies were chemotherapy (n = 6), radiotherapy (n = 1), and chemoradiotherapy (n = 17). Immunohistochemistry revealed positive expression of EGFR in 30.8%, Erk in 92.3%, p-Erk in 45.9%, Akt in 71.8%, and p-Akt in 20.5% of cases. On univariate analyses, tumor grade (P = .0098), p-Akt (P = .0003), and p-Erk (P = .0052) expression correlated with survival. On multivariate analyses, age (P = .0002; hazard ratio [HR], 1.8), grade (P = .00318; HR, 3.0), Akt (P = .0433; HR, .4), p-Akt (P = .0002; HR, .2), and p-Erk (P = .0003; HR, 3.5) expression correlated significantly with survival.


CONCLUSIONS
p-Erk and p-Akt expression may have prognostic and therapeutic implications in pancreatic cancer.
Chadha
Krishdeep S
KS
Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA.
Khoury
Thaer
T
Yu
Jihnhee
J
Black
Jennifer D
JD
Gibbs
John F
JF
Kuvshinoff
Boris W
BW
Tan
Dongfeng
D
Brattain
Michael G
MG
Javle
Milind M
MM
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000601:surgery*; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors
D019394:Ki-67 Antigen; C494918:AKT1 protein, human; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3