TY - JOUR
T1 - Akt expression may predict favorable prognosis in cholangiocarcinoma
AU - Javle, Milind M.
AU - Yu, Jihnhee
AU - Khoury, Thaer
AU - Chadha, Krishdeep C.
AU - Iyer, Renuka V.
AU - Foster, Jason
AU - Kuvshinoff, Boris W.
AU - Gibbs, John F.
AU - Geradts, Joseph
AU - Black, Jennifer D.
AU - Brattain, Michael G
PY - 2006/11
Y1 - 2006/11
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.
KW - Akt protein
KW - Biliary tract neoplasm
KW - Cholangiocarcinoma
KW - Cyclooxygenase-2 protein
KW - Epidermal growth factor receptor
KW - Gene
UR - http://www.scopus.com/inward/record.url?scp=33748764364&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748764364&partnerID=8YFLogxK
U2 - 10.1111/j.1440-1746.2006.04373.x
DO - 10.1111/j.1440-1746.2006.04373.x
M3 - Article
C2 - 16984600
AN - SCOPUS:33748764364
SN - 0815-9319
VL - 21
SP - 1744
EP - 1751
JO - Journal of Gastroenterology and Hepatology (Australia)
JF - Journal of Gastroenterology and Hepatology (Australia)
IS - 11
ER -