Expression of factors involved in regulation of DNA mismatch repair- and apoptosis pathways in ovarian cancer patients.
A major obstacle in treatment of ovarian cancer is intrinsic or acquired drug resistance causing failure of chemotherapy followed by a poor clinical outcome. Drug resistance of ovarian carcinoma can be caused by dysregulation of cellular factors involved in regulation of apoptosis and DNA repair pathways. In this study, 73 ovarian carcinoma specimens obtained before and after chemotherapy were analysed by immunohistochemistry for expression of seven proteins playing an important role in regulation of DNA mismatch repair and apoptosis. The prognostic significance of these proteins in the meaning of overall and progression-free survival was evaluated in univariate and multivariate analysis. Bcl-xL, hMSH2, caspase-3, p21 and p53 displayed prognostic importance in univariate analysis. Furthermore, it was demonstrated that caspase-3 and p21 were also independent prognostic markers for both, overall and progression-free survival. In conclusion, these data indicate that analysis of proteins involved in DNA mismatch repair and apoptosis can be useful for prediction of clinical outcome in ovarian carcinoma patients.
Materna
Verena
V
Institute of Pathology, Charité Campus Mitte, D-10117 Berlin, Germany.
Surowiak
Pawel
P
Markwitz
Ewa
E
Spaczynski
Marek
M
Drag-Zalesinska
Malgorzata
M
Zabel
Maciej
M
Lage
Hermann
H
D048868:Adaptor Proteins, Signal Transducing; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002352:Carrier Proteins / Q000096:biosynthesis; D053148:Caspase 3 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D053843:DNA Mismatch Repair; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D017671:Platinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051020:bcl-X Protein / Q000096:biosynthesis
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; C081876:CKAP4 protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; C501486:MLH1 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D017671:Platinum Compounds; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D053148:Caspase 3; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein