TY - JOUR
T1 - Mitogen-activated protein kinases (MAPK) as predictors of clinical outcome in serous ovarian carcinoma in effusions
AU - Givant-Horwitz, Vered
AU - Davidson, Ben
AU - Lazarovici, Philip
AU - Schaefer, Erik
AU - Nesland, Jahn M.
AU - Tropé, Claes G.
AU - Reich, Reuven
PY - 2003/10/1
Y1 - 2003/10/1
N2 - Objective. The objective was to investigate the expression (level) and phosphorylation status (activity) of the extracellular-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and high-osmolarity glycerol response kinase (p38), their role in the biology of ovarian carcinoma, and their correlation with chemotherapy response. Methods. Sixty-four fresh-frozen effusions from patients diagnosed with serous ovarian carcinoma were studied using immunoblotting. Results were analyzed for possible association with expression of proliferation and apoptosis markers, patient age, disease stage, tumor grade, histological grade, chemotherapy status, and survival. Results. p38 level correlated with younger age (P = 0.004), while that of JNK correlated with better tumor differentiation (P = 0.009). Higher expression of Pan-JNK (P = 0.018) and higher p-ERK activity (P = 0.014) were seen in postchemotherapy specimens, specifically related to treatment by platinum agents. pan-JNK expression was higher in specimens treated with both platinum agents (P = 0.038) and paclitaxel (P = 0.033). In univariate survival analysis, the level of pan-ERK (P = 0.002), pan-JNK (P = 0.045), and pan-p38 (P = 0.016), as well as p-ERK activity (P = 0.014) correlated with better overall survival. In Cox multivariate survival analysis, pan-ERK (P = 0.001), pan-p38 (P = 0.017), and p-ERK (P = 0.041) retained their predictive value. Conclusions. Our results present the first evidence of in vivo involvement of MAPKs in the clinical course of ovarian cancer and the possible effect of chemotherapy on intracellular signaling in this disease. The improved prognosis associated with expression and phosphorylation of all three mitogen-activated protein kinase families highlights the unique properties of cancer cells in effusions and may expand our understanding of the biology of ovarian carcinoma at this site, possibly affecting treatment strategies for this malignancy.
AB - Objective. The objective was to investigate the expression (level) and phosphorylation status (activity) of the extracellular-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and high-osmolarity glycerol response kinase (p38), their role in the biology of ovarian carcinoma, and their correlation with chemotherapy response. Methods. Sixty-four fresh-frozen effusions from patients diagnosed with serous ovarian carcinoma were studied using immunoblotting. Results were analyzed for possible association with expression of proliferation and apoptosis markers, patient age, disease stage, tumor grade, histological grade, chemotherapy status, and survival. Results. p38 level correlated with younger age (P = 0.004), while that of JNK correlated with better tumor differentiation (P = 0.009). Higher expression of Pan-JNK (P = 0.018) and higher p-ERK activity (P = 0.014) were seen in postchemotherapy specimens, specifically related to treatment by platinum agents. pan-JNK expression was higher in specimens treated with both platinum agents (P = 0.038) and paclitaxel (P = 0.033). In univariate survival analysis, the level of pan-ERK (P = 0.002), pan-JNK (P = 0.045), and pan-p38 (P = 0.016), as well as p-ERK activity (P = 0.014) correlated with better overall survival. In Cox multivariate survival analysis, pan-ERK (P = 0.001), pan-p38 (P = 0.017), and p-ERK (P = 0.041) retained their predictive value. Conclusions. Our results present the first evidence of in vivo involvement of MAPKs in the clinical course of ovarian cancer and the possible effect of chemotherapy on intracellular signaling in this disease. The improved prognosis associated with expression and phosphorylation of all three mitogen-activated protein kinase families highlights the unique properties of cancer cells in effusions and may expand our understanding of the biology of ovarian carcinoma at this site, possibly affecting treatment strategies for this malignancy.
KW - Chemotherapy
KW - Mitogen-activated protein kinases
KW - Ovarian carcinoma
KW - Serous effusions
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=0141534435&partnerID=8YFLogxK
U2 - 10.1016/S0090-8258(03)00434-7
DO - 10.1016/S0090-8258(03)00434-7
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C2 - 14529677
AN - SCOPUS:0141534435
SN - 0090-8258
VL - 91
SP - 160
EP - 172
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 1
ER -
