Activated Akt and Erk expression and survival after surgery in pancreatic carcinoma

Krishdeep S. Chadha, Thaer Khoury, Jihnhee Yu, Jennifer D Black, John F. Gibbs, Boris W. Kuvshinoff, Dongfeng Tan, Michael G Brattain, Milind M. Javle

Research output: Contribution to journalArticle

94 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)933-939
Number of pages7
JournalAnnals of Surgical Oncology
Volume13
Issue number7
DOIs
StatePublished - Jul 1 2006

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Epidermal Growth Factor Receptor
Survival
Pancreatic Neoplasms
Neoplasms
Pancreatectomy
Avidin
Chemoradiotherapy
Biotin
Immunoenzyme Techniques
Paraffin
Peroxidase
Pancreatic Carcinoma
Adenocarcinoma
Phosphotransferases
Radiotherapy
Therapeutics
Multivariate Analysis
Immunohistochemistry
Monoclonal Antibodies
Staining and Labeling

Keywords

  • Akt protein
  • Erk MAP kinase
  • Pancreatectomy
  • Pancreatic neoplasms

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Chadha, K. S., Khoury, T., Yu, J., Black, J. D., Gibbs, J. F., Kuvshinoff, B. W., ... Javle, M. M. (2006). Activated Akt and Erk expression and survival after surgery in pancreatic carcinoma. Annals of Surgical Oncology, 13(7), 933-939. https://doi.org/10.1245/ASO.2006.07.011

Activated Akt and Erk expression and survival after surgery in pancreatic carcinoma. / Chadha, Krishdeep S.; Khoury, Thaer; Yu, Jihnhee; Black, Jennifer D; Gibbs, John F.; Kuvshinoff, Boris W.; Tan, Dongfeng; Brattain, Michael G; Javle, Milind M.

In: Annals of Surgical Oncology, Vol. 13, No. 7, 01.07.2006, p. 933-939.

Research output: Contribution to journalArticle

Chadha, KS, Khoury, T, Yu, J, Black, JD, Gibbs, JF, Kuvshinoff, BW, Tan, D, Brattain, MG & Javle, MM 2006, 'Activated Akt and Erk expression and survival after surgery in pancreatic carcinoma', Annals of Surgical Oncology, vol. 13, no. 7, pp. 933-939. https://doi.org/10.1245/ASO.2006.07.011
Chadha, Krishdeep S. ; Khoury, Thaer ; Yu, Jihnhee ; Black, Jennifer D ; Gibbs, John F. ; Kuvshinoff, Boris W. ; Tan, Dongfeng ; Brattain, Michael G ; Javle, Milind M. / Activated Akt and Erk expression and survival after surgery in pancreatic carcinoma. In: Annals of Surgical Oncology. 2006 ; Vol. 13, No. 7. pp. 933-939.
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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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AU - Khoury, Thaer

AU - Yu, Jihnhee

AU - Black, Jennifer D

AU - Gibbs, John F.

AU - Kuvshinoff, Boris W.

AU - Tan, Dongfeng

AU - Brattain, Michael G

AU - Javle, Milind M.

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N2 - 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.

AB - 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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KW - Erk MAP kinase

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