Prognostic Impact of p53, p27, and C-MYC on Clinicopathological Features and Outcome in Early-Stage (FIGO I-II) Epithelial Ovarian Cancer (original) (raw)

Prognostic Impact of p53, p27, and C-MYC on Clinicopathological Features and Outcome in Early-Stage (FIGO I-II) Epithelial Ovarian Cancer

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  1. Ingirídur Anna Skírnisdóttir, MD, PhD*,
  2. Bengt Sorbe, MD, PhD†,
  3. Katarina Lindborg, MD* and
  4. Tomas Seidal, MD, PhD‡
  5. * Department of Women's and Children's Health, Obstetrics and Gynecology, Uppsala University, Uppsala;
  6. † Department of Gynecological Oncology, Örebro University Hospital, Örebro;
  7. ‡ Department of Pathology, Halmstad Medical Center Hospital, Halmstad, Sweden.
  8. Address correspondence and reprint requests to Ingirídur Anna Skírnisdóttir, MD, PhD, Department of Gynecology and Obstetrics, University Hospital, Akademiska sjukhuset, SE-751 85 Uppsala, Sweden. E-mail: ingiridur.skirnisdottir{at}kbh.uu.se.

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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