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Activated Akt and Erk Expression and Survival After Surgery in Pancreatic Carcinoma

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Abstract

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.

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Acknowledgments

The authors thank Donna Oleszek for performing immunohistochemical staining for EGFR signaling intermediates. Supported by National Institutes of Health grants CA62502 and CA16056.

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Authors and Affiliations

  1. Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, 14263

    Krishdeep S. Chadha MD & Milind M. Javle MD

  2. Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, 14263

    Thaer Khoury MD & Dongfeng Tan MD

  3. Department of Biostatistics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, 14263

    Jihnhee Yu PhD

  4. Department of Pharmacology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, 14263

    Jennifer D. Black PhD & Michael G. Brattain PhD

  5. Department of Surgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, 14263

    John F. Gibbs MD & Boris W. Kuvshinoff MD

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  1. Krishdeep S. Chadha MD
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  2. Thaer Khoury MD
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  3. Jihnhee Yu PhD
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  4. Jennifer D. Black PhD
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  5. John F. Gibbs MD
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  6. Boris W. Kuvshinoff MD
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  7. Dongfeng Tan MD
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  8. Michael G. Brattain PhD
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  9. Milind M. Javle MD
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Correspondence to Milind M. Javle MD.

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Chadha, K.S., Khoury, T., Yu, J. et al. Activated Akt and Erk Expression and Survival After Surgery in Pancreatic Carcinoma. Ann Surg Oncol 13, 933–939 (2006). https://doi.org/10.1245/ASO.2006.07.011

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  • DOI: https://doi.org/10.1245/ASO.2006.07.011

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