Prognostic and Pathogenetic Relevance of Embryonal Stem Cell Factors for Serous Ovarian Neoplasms
Anna Fischer, Deborah Pham, Petra Bareiss, Cornelia Bachmann, Hans Neubauer, Falko Fend, Claudia Lengerke, Sven Perner, Tanja Fehm, Annette Staebler. University of Tuebingen, Tuebingen, Germany; University of Bonn, Bonn, Germany
Background: Primary resistance to chemotherapy and recurrent disease are the major causes of death for patients with ovarian carcinoma. Tumor stem cells and reexpression of stem cell factors are thought to contribute to both processes Expression of stem cell markers like Sox2 and ALDH-1 was already found in several solid tumors. In this study we performed a comprehensive analysis of Sox2, Nanog and Oct4 as well as ALDH-1, Ki-67, Cyclin D1 in serous ovarian tumors.
Design: 149 cases of ovarian serous carcinoma and 28 serous borderline tumors were analyzed by immunohistochemistry in a tissue microarray. Sox2, Oct4, Nanog, ALDH-1 and Cyclin D1 were evaluated in a semiquantitative score (0=0% positive cells, 1+ = 1-10% positive cells, 2+ = 11-50%, 3+ =51-80%, 4+ = >80% positive cells). For Mib-1/Ki67 the percentage of positive cells was analyzed by counting at least 100 nuclei. Coexpression and correlation of the markers were analyzed. Overall survival was compared by Kaplan-Meier analysis.
Results: For expression of Sox2 we find a significant association with high-grade serous carcinomas if compared to low-grade carcinomas or borderline tumors. We find no correlation between the expression of Sox2 and expression of ALDH-1, Cyclin D1 or Ki67. However, we find a significant correlation between expression of ALDH-1 and Ki67, indicating a role of ALDH-1 in cell proliferation independent from the stem cell phenotype. There was no detectable expression of Oct4 or Nanog. Survival analysis of high-grade serous carcinomas stage II-IV showed a favourable effect of Sox2 expression on recurrence free survival (median survival 27 months vs. 21 months, p= 0.041) and a positive, but not significant effect on overall survival (39 vs. 25 months, p=0,062). For ALDH-1, however, we demonstrate no effect on recurrence free or overall survival.
Conclusions: Expression of embryonal stem cell factors SOX2 and ALDH-1 can be detected in serous ovarian tumors. We find association of different tumor characteristics with these factors like poor differentiation and improved survival with SOX2 and increased proliferation rate with ALDH. These findings suggest, that expression of several embryonal stem cell factors in serous ovarian tumors does not reflect a unique stem cell phenotype, but rather may show divergent association with biological and clinical parameters.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 208, Wednesday Afternoon