Akt expression may predict favorable prognosis in cholangiocarcinoma

Milind M. Javle, Jihnhee Yu, Thaer Khoury, Krishdeep C. Chadha, Renuka V. Iyer, Jason M Foster, Boris W. Kuvshinoff, John F. Gibbs, Joseph Geradts, Jennifer D Black, Michael G Brattain

Research output: Contribution to journalArticle

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Abstract

Background: Overexpression of signaling proteins including epidermal growth factor receptor (EGFR), Akt, mitogen activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) occurs in cholangiocarcinoma cell lines. However, the prognostic value of these markers is unknown. No prior study correlated the expression of these signaling proteins with clinical outcome. Further, co-expression of these proteins has not been reported. Co-expression may reflect cross-talk between signaling pathways. The aim of this clinicopathological study was to investigate the overexpression and co-expression of EGFR and related signaling proteins in cholangiocarcinoma and explore their relationship to clinical outcome. Methods: Twenty-four consecutive cases of cholangiocarcinoma treated from 1996 to 2002 at Roswell Park Cancer Institute were included. Immunohistochemical staining of paraffin-embedded tissue sections was performed using antibodies against Akt, p-Akt, MAPK, p-MAPK, COX-2, EGFR and p-EGFR. Two pathologists independently scored the protein expression. Results: Cyclooxygenase-2, Akt, and p-MAPK were commonly expressed in biliary cancers (100%, 96% and 87% of malignant cells, respectively). EGFR (60%) and p-EGFR (22%) overexpression was also detected. There was a significant association between EGFR and p-EGFR (P = 0.027) and between Akt and p-Akt (P = 0.017) expression in tumor tissue. A noteworthy association was shown between MAPK and p-Akt (P = 0.054). Multivariate analysis using the Cox proportional hazard model identified the use of chemotherapy (hazard ratio [HR] = 0.039, P = 0.0002), radiation (HR = 0.176, P = 0.0441) and Akt expression (HR = 0.139, P = 0.006) as the best predictors of overall prognosis. Conclusion: Epidermal growth factor receptor signaling intermediates are commonly expressed in cholangiocarcinoma. Expression of Akt and use of systemic chemotherapy or radiation may correlate with improved survival.

Original languageEnglish (US)
Pages (from-to)1744-1751
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume21
Issue number11
DOIs
StatePublished - Jan 1 2006

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Cholangiocarcinoma
Epidermal Growth Factor Receptor
Cyclooxygenase 2
Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Proteins
Biliary Tract Neoplasms
Radiation
Drug Therapy
Proportional Hazards Models
Paraffin
Neoplasms
Multivariate Analysis
Staining and Labeling
Cell Line
Antibodies

Keywords

  • Akt protein
  • Biliary tract neoplasm
  • Cholangiocarcinoma
  • Cyclooxygenase-2 protein
  • Epidermal growth factor receptor
  • Gene

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Akt expression may predict favorable prognosis in cholangiocarcinoma. / Javle, Milind M.; Yu, Jihnhee; Khoury, Thaer; Chadha, Krishdeep C.; Iyer, Renuka V.; Foster, Jason M; Kuvshinoff, Boris W.; Gibbs, John F.; Geradts, Joseph; Black, Jennifer D; Brattain, Michael G.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 21, No. 11, 01.01.2006, p. 1744-1751.

Research output: Contribution to journalArticle

Javle, MM, Yu, J, Khoury, T, Chadha, KC, Iyer, RV, Foster, JM, Kuvshinoff, BW, Gibbs, JF, Geradts, J, Black, JD & Brattain, MG 2006, 'Akt expression may predict favorable prognosis in cholangiocarcinoma', Journal of Gastroenterology and Hepatology (Australia), vol. 21, no. 11, pp. 1744-1751. https://doi.org/10.1111/j.1440-1746.2006.04373.x
Javle, Milind M. ; Yu, Jihnhee ; Khoury, Thaer ; Chadha, Krishdeep C. ; Iyer, Renuka V. ; Foster, Jason M ; Kuvshinoff, Boris W. ; Gibbs, John F. ; Geradts, Joseph ; Black, Jennifer D ; Brattain, Michael G. / Akt expression may predict favorable prognosis in cholangiocarcinoma. In: Journal of Gastroenterology and Hepatology (Australia). 2006 ; Vol. 21, No. 11. pp. 1744-1751.
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abstract = "Background: Overexpression of signaling proteins including epidermal growth factor receptor (EGFR), Akt, mitogen activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) occurs in cholangiocarcinoma cell lines. However, the prognostic value of these markers is unknown. No prior study correlated the expression of these signaling proteins with clinical outcome. Further, co-expression of these proteins has not been reported. Co-expression may reflect cross-talk between signaling pathways. The aim of this clinicopathological study was to investigate the overexpression and co-expression of EGFR and related signaling proteins in cholangiocarcinoma and explore their relationship to clinical outcome. Methods: Twenty-four consecutive cases of cholangiocarcinoma treated from 1996 to 2002 at Roswell Park Cancer Institute were included. Immunohistochemical staining of paraffin-embedded tissue sections was performed using antibodies against Akt, p-Akt, MAPK, p-MAPK, COX-2, EGFR and p-EGFR. Two pathologists independently scored the protein expression. Results: Cyclooxygenase-2, Akt, and p-MAPK were commonly expressed in biliary cancers (100{\%}, 96{\%} and 87{\%} of malignant cells, respectively). EGFR (60{\%}) and p-EGFR (22{\%}) overexpression was also detected. There was a significant association between EGFR and p-EGFR (P = 0.027) and between Akt and p-Akt (P = 0.017) expression in tumor tissue. A noteworthy association was shown between MAPK and p-Akt (P = 0.054). Multivariate analysis using the Cox proportional hazard model identified the use of chemotherapy (hazard ratio [HR] = 0.039, P = 0.0002), radiation (HR = 0.176, P = 0.0441) and Akt expression (HR = 0.139, P = 0.006) as the best predictors of overall prognosis. Conclusion: Epidermal growth factor receptor signaling intermediates are commonly expressed in cholangiocarcinoma. Expression of Akt and use of systemic chemotherapy or radiation may correlate with improved survival.",
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AU - Yu, Jihnhee

AU - Khoury, Thaer

AU - Chadha, Krishdeep C.

AU - Iyer, Renuka V.

AU - Foster, Jason M

AU - Kuvshinoff, Boris W.

AU - Gibbs, John F.

AU - Geradts, Joseph

AU - Black, Jennifer D

AU - Brattain, Michael G

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N2 - Background: Overexpression of signaling proteins including epidermal growth factor receptor (EGFR), Akt, mitogen activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) occurs in cholangiocarcinoma cell lines. However, the prognostic value of these markers is unknown. No prior study correlated the expression of these signaling proteins with clinical outcome. Further, co-expression of these proteins has not been reported. Co-expression may reflect cross-talk between signaling pathways. The aim of this clinicopathological study was to investigate the overexpression and co-expression of EGFR and related signaling proteins in cholangiocarcinoma and explore their relationship to clinical outcome. Methods: Twenty-four consecutive cases of cholangiocarcinoma treated from 1996 to 2002 at Roswell Park Cancer Institute were included. Immunohistochemical staining of paraffin-embedded tissue sections was performed using antibodies against Akt, p-Akt, MAPK, p-MAPK, COX-2, EGFR and p-EGFR. Two pathologists independently scored the protein expression. Results: Cyclooxygenase-2, Akt, and p-MAPK were commonly expressed in biliary cancers (100%, 96% and 87% of malignant cells, respectively). EGFR (60%) and p-EGFR (22%) overexpression was also detected. There was a significant association between EGFR and p-EGFR (P = 0.027) and between Akt and p-Akt (P = 0.017) expression in tumor tissue. A noteworthy association was shown between MAPK and p-Akt (P = 0.054). Multivariate analysis using the Cox proportional hazard model identified the use of chemotherapy (hazard ratio [HR] = 0.039, P = 0.0002), radiation (HR = 0.176, P = 0.0441) and Akt expression (HR = 0.139, P = 0.006) as the best predictors of overall prognosis. Conclusion: Epidermal growth factor receptor signaling intermediates are commonly expressed in cholangiocarcinoma. Expression of Akt and use of systemic chemotherapy or radiation may correlate with improved survival.

AB - Background: Overexpression of signaling proteins including epidermal growth factor receptor (EGFR), Akt, mitogen activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) occurs in cholangiocarcinoma cell lines. However, the prognostic value of these markers is unknown. No prior study correlated the expression of these signaling proteins with clinical outcome. Further, co-expression of these proteins has not been reported. Co-expression may reflect cross-talk between signaling pathways. The aim of this clinicopathological study was to investigate the overexpression and co-expression of EGFR and related signaling proteins in cholangiocarcinoma and explore their relationship to clinical outcome. Methods: Twenty-four consecutive cases of cholangiocarcinoma treated from 1996 to 2002 at Roswell Park Cancer Institute were included. Immunohistochemical staining of paraffin-embedded tissue sections was performed using antibodies against Akt, p-Akt, MAPK, p-MAPK, COX-2, EGFR and p-EGFR. Two pathologists independently scored the protein expression. Results: Cyclooxygenase-2, Akt, and p-MAPK were commonly expressed in biliary cancers (100%, 96% and 87% of malignant cells, respectively). EGFR (60%) and p-EGFR (22%) overexpression was also detected. There was a significant association between EGFR and p-EGFR (P = 0.027) and between Akt and p-Akt (P = 0.017) expression in tumor tissue. A noteworthy association was shown between MAPK and p-Akt (P = 0.054). Multivariate analysis using the Cox proportional hazard model identified the use of chemotherapy (hazard ratio [HR] = 0.039, P = 0.0002), radiation (HR = 0.176, P = 0.0441) and Akt expression (HR = 0.139, P = 0.006) as the best predictors of overall prognosis. Conclusion: Epidermal growth factor receptor signaling intermediates are commonly expressed in cholangiocarcinoma. Expression of Akt and use of systemic chemotherapy or radiation may correlate with improved survival.

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