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The prognostic importance ofp53, bcl-2, and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
2002 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 3, 265-276 p.Article in journal (Refereed) Published
Abstract [en]

Epithelial ovarian cancer is one of the major causes of death among women. The increasing knowledge about molecular events involved in the early stages of ovarian tumorigenesis may provide the basis for management in the future. In a series of 109 patients with epithelial carcinomas in FIGO stages IA-IIC, a number of clinicopathologic prognostic factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to the biologic factors p53, bcl-2, and bax, which are important regulators of apoptosis. Immunohistochemical techniques were used. All the patients received adjuvant chemotherapy after the primary surgery. Univariate analysis showed that expression of p53 was significantly associated with tumor grade (P = 0.014), probability of persistent disease (P = 0.016), and cancer-specific survival rate (P = 0.007). Positive bcl-2 staining was associated with endometrioid tumor subtype (P = 0.029) and a favorable tumor grade distribution (P = 0.034), but not with the survival status. The combined p53-bcl-2 expression was related to histopathologic subtype (P = 0.032), tumor grade (P = 0.011), persistent disease (P = 0.014), and risk of dying due to the disease (P = 0.039). The bax status was not a prognostic factor, but the combined p53-bax expression showed an association with FIGO stage (P = 0.014), tumor grade (P = 0.034), persistent disease (P = 0.006), and risk of dying due to the disease (P = 0.039). The combined bcl-2-bax expression was related to histopathologic subtype (P = 0.045) and tumor grade (P = 0.022). In a multivariate Cox analysis, tumor grade (P = 0.014), and p53 status (P = 0.020) were independent and significant prognostic factors with regard to the cancer-specific survival rate.

Place, publisher, year, edition, pages
2002. Vol. 12, no 3, 265-276 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-89644PubMedID: 12060448OAI: oai:DiVA.org:uu-89644DiVA: diva2:161302
Available from: 2002-02-21 Created: 2002-02-21 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Prognostic Factors in Early Stages (FIGO I-II) of Epithelial Ovarian Carcinoma
Open this publication in new window or tab >>Prognostic Factors in Early Stages (FIGO I-II) of Epithelial Ovarian Carcinoma
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

From January, 1988, to December, 1993, 113 patients with FIGO stage IA-IIC epithelial ovarian carcinoma were treated with postoperative radiotherapy. The median follow-up period was 74 months. Tumor recurrences were recorded in 33 cases (30%). The cancer-specific survival rate was 72%. Tumor grade was a significant (P = 0.007) and independent prognostic factor in the multivariate analysis. In a smaller series of 106 patients, a number of prognostic factors (age, FIGO stage, histopathological type, and tumor grade) were studied in relation to regulators of apoptosis (p53, bcl-2, and bax) and growth factor receptors (HER-2/neu and EGFR). Immunohistochemical techniques were used. In a separate series of 103 patients, the DNA content (flow cytometry) and p53 status of the tumors were also studied and related to the same clinicopathological factors. P53 was associated with tumor grade (P = 0.007) and survival status (P = 0.046). In a Cox multivariate analysis, tumor grade (P = 0.0006), bax status (P = 0.020), and EGFR status (P = 0.018) were significant and independent prognostic factors. DNA ploidy of the tumors was strongly associated with tumor grade.

From January, 1994, to December, 1998, a series of 109 patients with ovarian carcinomas (FIGO IA-IIC) were treated with postoperative adjuvant chemotherapy. The same prognostic factors were studied in this series. The median follow-up was 48 months and the cancer-specific survival rate was 75%. Twenty-five (25%) tumor recurrences were recorded. The most favorable survival rate was seen in patients with tumors negative for p53 and positive for bcl-2 or bax. In a multivariate analysis, tumor grade (P = 0.014) and p53 status (P = 0.020) were independent prognostic factors.

Clinical, histopathological and biological prognostic factors should be combined in prognostic models to render patient-tailored therapy possible and to define different prognostic groups for future clinical studies of adjuvant therapy in early stage ovarian carcinomas.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 88 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1123
Keyword
Obstetrics and gynaecology, Ovarian cancer, early stages, adjuvant therapy, prognosis, tumor grade, apoptotic regulators, p53, bcl-2, bax, growth factor receptors, HER-2/neu, EGFR, DNA ploidy, Obstetrik och kvinnosjukdomar
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-1729 (URN)91-554-5235-3 (ISBN)
Public defence
2002-03-15, Rosénsalen, UAS, Uppsala, 09:15
Opponent
Available from: 2002-02-21 Created: 2002-02-21Bibliographically approved

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