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Original Article |
1 Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263
2 Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263
3 Department of Biostatistics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263
4 Department of Pharmacology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263
5 Department of Surgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263
Correspondence: Address correspondence and reprint requests to: Milind M. Javle, MD; E-mail: milind.javle{at}roswellpark.org.
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.
Key Words: Pancreatic neoplasms • Pancreatectomy • Akt protein • Erk MAP kinase
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