TY - JOUR
T1 - Osteopontin, E-cadherin, and β-catenin expression as prognostic biomarkers in patients with radically resected gastric cancer
AU - Di Bartolomeo, Maria
AU - Pietrantonio, Filippo
AU - Pellegrinelli, Alessandro
AU - Martinetti, Antonia
AU - Mariani, Luigi
AU - Daidone, Maria Grazia
AU - Bajetta, Emilio
AU - Pelosi, Giuseppe
AU - de Braud, Filippo
AU - Floriani, Irene
AU - Miceli, Rosalba
PY - 2015/4/11
Y1 - 2015/4/11
N2 - A correlation between osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 overexpression and poor clinicopathological features and prognosis has been previously suggested in gastric cancer. This translational study was aimed at assessing the correlation of these immunohistochemical biomarkers with outcome in patients with radically resected gastric cancer. We analyzed osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 expression by immunohistochemistry in 346 primary gastric tumor tissue samples from patients enrolled in the ITACA-S trial. This phase III study randomized patients with radically resected gastric cancer to receive adjuvant chemotherapy with either 5-fluorouracil and leucovorin or a sequential regimen of infusional 5-fluorouracil and leucovorin plus irinotecan followed by cisplatin and docetaxel. High expression of osteopontin was correlated with high histological grade, diffuse histotype, and peritoneal relapse, but not with TNM stage. Moreover, osteopontin overexpression was associated with higher risk of tumor recurrence and metastases, and was an independent prognostic factor for both relapse-free and overall survival of gastric cancer patients following adjuvant chemotherapy. Abnormal E-cadherin expression and abnormal β-catenin expression were correlated with more advanced disease stage, and as a consequence, with poor outcome. Our results suggest that osteopontin overexpression is a valuable independent predictor of tumor recurrence and survival in patients with radically resected gastric cancer.
AB - A correlation between osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 overexpression and poor clinicopathological features and prognosis has been previously suggested in gastric cancer. This translational study was aimed at assessing the correlation of these immunohistochemical biomarkers with outcome in patients with radically resected gastric cancer. We analyzed osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 expression by immunohistochemistry in 346 primary gastric tumor tissue samples from patients enrolled in the ITACA-S trial. This phase III study randomized patients with radically resected gastric cancer to receive adjuvant chemotherapy with either 5-fluorouracil and leucovorin or a sequential regimen of infusional 5-fluorouracil and leucovorin plus irinotecan followed by cisplatin and docetaxel. High expression of osteopontin was correlated with high histological grade, diffuse histotype, and peritoneal relapse, but not with TNM stage. Moreover, osteopontin overexpression was associated with higher risk of tumor recurrence and metastases, and was an independent prognostic factor for both relapse-free and overall survival of gastric cancer patients following adjuvant chemotherapy. Abnormal E-cadherin expression and abnormal β-catenin expression were correlated with more advanced disease stage, and as a consequence, with poor outcome. Our results suggest that osteopontin overexpression is a valuable independent predictor of tumor recurrence and survival in patients with radically resected gastric cancer.
KW - Adjuvant chemotherapy
KW - Biomarker
KW - Gastric cancer
KW - Osteopontin
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=84927555675&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84927555675&partnerID=8YFLogxK
U2 - 10.1007/s10120-015-0495-y
DO - 10.1007/s10120-015-0495-y
M3 - Article
AN - SCOPUS:84927555675
JO - Gastric Cancer
JF - Gastric Cancer
SN - 1436-3291
ER -