| 1. |
- Skírnisdóttir, Ingiridur, 1951-, et al.
(författare)
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Differences in Clinical and Biological Features Between Type I and Type II Tumors in FIGO Stages I-II Epithelial Ovarian Carcinoma.
- 2015
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Ingår i: International Journal of Gynecological Cancer. - 1048-891X .- 1525-1438. ; 25:7, s. 1239-47
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of this study was to compare immunohistochemical profile for the apoptosis regulators p53, C-MYC, bax, PUMA, and PTEN and the cell cycle regulatory proteins p21 and p27, as well as clinical factors between types I and II tumors.METHODS: In total, 131 patients in FIGO (International Federation of Gynecology and Obstetrics) stages I-II were divided into 2 groups of patients after type I tumors (n = 79) and type II tumors (n = 52). Differences in the immunohistochemical profile for the cell cycle-related proteins, detected by tissue microarrays and immune-histochemistry, were compared. For statistical tests, the Pearson χ test and the logistic regression model were used. All tests were 2-sided, and the level of statistical significance was P ≤ 0.05.RESULTS: In multivariate logistic regression analysis with recurrent disease as endpoint, FIGO stage (odds ratio [OR], 4.7), type I/II tumors (OR, 3.8), body mass index (BMI) (OR, 3.5), and p53 status (OR, 4.2) all were found to be independent predictive factors. In 2 different multivariate logistic regression analyses with type I/II tumors as endpoint, both p53p21 (OR, 2.9) and p27 status (OR, 3.0) were associated with type II tumors. Differently, C-MYC status (OR, 0.4) was associated with type I tumors. Furthermore, age (OR, 1.04), BMI (OR, 0.4), and recurrent disease (OR, 4.3) all were associated to type II tumors. In survival analysis, there was a trend (P = 0.054) toward better disease-free survival for patients with type I tumors.CONCLUSIONS: Concomitant positivity for p53 and negativity for p21, positivity for p27, and negativity for C-MYC in an epithelial ovarian tumor might strengthen the diagnostic option of type II tumor ovarian carcinoma. Patients with type II tumors were older, had lower BMI, and had more often recurrent disease than patients with type I tumors.
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| 2. |
- Skirnisdottir, Ingiridur, et al.
(författare)
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Prognostic Impact of Concomitant p53 and PTEN on Outcome in Early Stage (FIGO I-II) Epithelial Ovarian Cancer
- 2011
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Ingår i: International Journal of Gynecological Cancer. - 1048-891X .- 1525-1438. ; 21:6, s. 1024-1031
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The objective of the study was to evaluate the prognostic effect of p53, PTEN, and concomitant p53 PTEN status on clinicopathologic features, recurrent disease, and disease-free survival (DFS) of 131 patients in FIGO stages I to II with epithelial ovarian cancer. Methods: The technique of tissue microarray and immunohistochemistry was used for the detection of positivity of the biologic markers p53 and PTEN. Results: In the complete series, the 5-year DFS rate was 68%, and the overall survival rate was 71%. Positive staining for p53 and PTEN was detected in 25% and 22% of cases, respectively. Positivity of p53 was associated with tumor grade in the total series but not in the subgroup of serous tumors. In survival analysis, there was worse survival (P = 0.003) in the group of patients with p53-positive tumors compared with the group of patients with p53-negative tumors with DFS of 62% and 82%, respectively. Furthermore, DFS was 15% for the subgroup of patients with concomitant p53-positivity and PTEN-negativity of tumors compared with DFS of 62% for others in 1 group (p53+PTEN+, p53-PTEN+, p53-PTEN-) at 100 months. The difference was highly significant (P = 0.006). FIGO stage (odds ratio = 8.0) and p53 PTEN status (odds ratio = 0.6) were predictive factors for tumor recurrences in a logistic regression and prognostic factors with hazard ratios (HRs) of 4.0 and 0.6, respectively, in a multivariate Cox regression analysis. In a separate Cox regression analysis, FIGO stage (HR = 3.6) and p53 status (HR = 2.0) were prognostic factors for DFS. For serous tumors (n = 51) recurrent disease was associated with FIGO stage (P = 0.013), and p53 loss (P = 0.029) but not with FIGO grade (P = 0.169). Conclusions: p53 status divides ovarian carcinomas into 2 subgroups after prognosis, also in serous tumors. Presence of PTEN in p53-positive tumors seems to protect from bad prognosis and absence of PTEN seems to worsen prognosis in early stages.
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| 3. |
- Skírnisdottir, Ingiridur, 1951-, et al.
(författare)
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Prognostic Impact of p53, p27, and C-MYC on Clinicopathological Features and Outcome in Early-Stage (FIGO I-II) Epithelial Ovarian Cancer
- 2011
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Ingår i: International Journal of Gynecological Cancer. - 1048-891X .- 1525-1438. ; 21:2, s. 236-244
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The objective of the study was to evaluate the prognostic effect of p53, p27, and C-MYC on clinicopathological features, recurrent disease, and disease-free survival (DFS) of 131 patients with ovarian cancer in International Federation of Gynecology and Obstetrics (FIGO) stages I-II. Methods: The technique of tissue microarray and immunohistochemistry was used for detection of positivity/overexpression of the biological markers p53, p27, and C-MYC. Results: In the complete series, the 5-year and overall survival rates were 68% and 71%, respectively. Positive staining for p53, p27, and C-MYC was detected in 25%, 57%, and 76% of cases, respectively. Positivity of p53, p27, concomitant p53-p27, C-MYC, and C-MYC-p27 status were associated with tumor grade. Positivity of p27 and concomitant p53-p27 were related to serous tumors. In survival analysis, DFS was related to p53, combined p53-p27, and combined p53-C-MYC status. Significant predictive factors for tumor recurrences were the FIGO stage (odds ratio [OR] = 9.8), status of node sampling (OR = 0.2), and p53 status (OR = 3.7) in a logistic regression analysis. In a multivariate Cox regression analysis, FIGO stage (hazard ratio [HR] = 4.3) and p53 status (HR = 3.0) were significant prognostic factors for DFS. In a separate Cox regression analysis, FIGO stage (HR = 2.0) and concomitant p53-p27-C-MYC status (HR = 0.3) were independent prognostic factors for DFS. It was possible to identify a subgroup, constituting 30% of the patients, who had excellent survival with tumors of concomitant p53 negativity, p27 positivity, and C-MYC positivity apart from the clinicopathological factors. Patients in this subgroup were longtime survivors with DFS of 92% at 5 and 9 years. Conclusions: The results of this study strongly suggest that patients with p53-positive tumors (alone/or combined with p27 and/or C-MYC) had significantly worse survival (DFS) compared with patients with p53-negative tumors. Patients with p53-positive tumors continued to have recurrences after the 5-year follow-up and die in disease.
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| 4. |
- Skírnisdóttir, Ingirídur, et al.
(författare)
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The prognostic importance ofp53, bcl-2, and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy
- 2002
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Ingår i: International Journal of Gynecological Cancer. - 1048-891X .- 1525-1438. ; 12:3, s. 265-276
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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