title: The apoptosis regulators p53, bax and PUMA: Relationship and impact             on outcome in early stage (FIGO I-II) ovarian carcinoma after post-surgical taxane-based             treatment.
abstract: The objective of this study was to evaluate the prognostic effect of the             apoptosis regulators p53, bax and PUMA for recurrent disease and disease-free             survival (DFS) in a series of 105 patients in FIGO-stages I-II with epithelial             ovarian cancer, all treated with post-surgical platinum-taxane chemotherapy. For             the detection of positivity of the biological markers p53, bax and PUMA the techniques             of tissue microarrays and immunohistochemistry (IHC) were used. In tumors the             frequency of p53 positivity was 24%, that of bax positivity was 83%, and strong             positivity was found for PUMA (43%). The bax status was related to tumor grade             (P=0.029). Positive staining for bax was related to strong positivity of PUMA             in the tumors (P=0.004). The p53, bax or PUMA status alone or concomitant (p53             bax, p53 PUMA and bax PUMA) were not related to age, histopathological subtype,             serous/non-serous tumors or type of the staging procedure at primary surgery.             In survival analysis p53-positive tumors (P=0.014) and concomitant p53-positive             and weak PUMA-positive tumors (P=0.015) were significantly correlated with shorter             DFS. Concomitant p53-negative and bax-positive tumors were significantly correlated             with longer survival (P=0.019). FIGO-stage (OR=6.0) and p53 status (OR=4.1) were             predictive factors for tumor recurrence in logistic regression analysis and independent             prognostic factors (HR=2.4 for both) in multivariate Cox regression analysis.             In a separate Cox multivariate regression analysis the p53 bax status (HR=2.2)             was an independent prognostic factor for DFS. The p53 PUMA status (HR=0.4) was             not an independent prognostic factor, however, a borderline significance (P=0.07)             was noted. Our results indicate that FIGO stage and p53 status alone were independent             predictive factors for recurrence and prognostic factors for survival. Furthermore,             p53 bax status was an independent prognostic factor for survival in this study.
authors.affiliation: Department of Women's and Children's Health, Uppsala University Hospital, Akademiska Sjukhuset, SE-751 85 Uppsala, Sweden. ingiridur.skirnisdottir@kbh.uu.se
authors.forename: I
authors.initials: I
authors.lastname: Skírnisdóttir
authors.forename: T
authors.initials: T
authors.lastname: Seidal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C080625:taxane