CD133 expression associated with poor prognosis in ovarian cancer

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Modern Pathology (Impact Factor: 6.19). 11/2011; 25(3):456-64. DOI: 10.1038/modpathol.2011.170
Source: PubMed


As a putative marker for cancer stem cells in human malignant tumors, including ovarian cancer, CD133 expression may define a tumor-initiating subpopulation of cells and is associated with the clinical outcome of patients. However, at this time its clinical significance in ovarian cancer remains uncertain. The aim of this study was to clarify the clinical role of CD133 expression in human ovarian cancer. Immunohistochemical staining of CD133 expression was performed in 400 ovarian carcinoma samples using tissue microarray. The associations among CD133 expression and clinical factors (diagnosis, tumor grade, cancer stage, and clinical response to chemotherapy), overall survival and disease-free survival time were analyzed. CD133 expression was found in 31% of ovarian carcinoma samples. Fisher's exact test and one-way analysis of variance suggested that CD133 expression was associated with high-grade serous carcinoma (P=0.035), late-stage disease (P<0.001), ascites level (P=0.010), and non-response to chemotherapy (P=0.023). CD133 expression was also associated with shorter overall survival time (P=0.007) and shorter disease-free survival time (P<0.001) by log-rank test. Moreover, CD133 expression was an independent predictor of shorter disease-free survival time in an unconditional logistic regression analysis with multiple covariates (P=0.024). Our results thus show that CD133 expression is a predictor of poor clinical outcome for patients with ovarian cancer, supporting the proposed link between CD133 and cancer stem cells.

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    • "CD133+ ovarian tumor cells were characterized by a higher proliferative potential and clonogenic efficiency than negative cells. For instance CD133 expression, in ovarian carcinoma samples, is related to a poor prognosis, including shorter overall and disease-free survival 56. The percentages of CD133-1/CD133-2 epitopes expressing cells were significantly lower in normal ovaries/benign tumors with respect to those expressed in ovarian carcinomas. "
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    ABSTRACT: Currently we are more and more improving our knowledge about the characteristics and the role of cancer stem cells in human cancer. Particularly we have realized that self-renewing ovarian cancer stem cells (CSCs) or ovarian cancer-initiating cells, and mesenchymal stem cells (SCs) too, are probably implicated in the etiopathogenesis of epithelial ovarian cancer (EOC). There is clear evidence that these cells are also involved in its intra- and extra-peritoneal diffusion and in the occurrence of chemo-resistance. In assessing the molecular characteristics of ovarian CSCs, we have to take note that these cellular populations are rare and the absence of specific cell surface markers represents a challenge to isolate and identify pure SC populations. In our review, we focused our attention on the molecular characteristics of epithelial ovarian CSCs and on the methods to detect them starting from their biological features. The study of ovarian CSCs is taking on an increasingly important strategic role, mostly for the potential therapeutic application in the next future.
    Journal of Cancer 03/2014; 5(5):301-310. DOI:10.7150/jca.8610 · 3.27 Impact Factor
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    • "As regards the role of CD133 expression in ovarian cancer, Ferrandina et al were the first to report that ovarian tumor samples to express CD133 [29] and that its expression did not provide any additional prognostic information for ovarian cancer patients [30] as no difference in time to progression and overall survival between cases with negative versus positive CD133 expression. On the contrary, recent data [31] have been published in a larger series of tumor ovarian samples suggesting that CD133 expression was associated with highgrade serous carcinoma, late-stage disease, with shorter disease free survival time and lack of response to chemotherapy (400 samples versus 160 of Ferrandina et al [30]). Our data agree with the ones reported by Ferrandina, even if the methodologies used are different (IHC in paraffin-embedded tissues versus FACS analysis in fresh tumor samples). "
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    ABSTRACT: The prognostic/predictive role of both CD133 and Aldehyde dehydrogenase (ALDH) expression in human ovarian cancer remains elusive. This is an observational study that investigated the expression of CD133 and of ALDH enzymatic activity in fresh ovarian cancer samples and their association with different clinic-pathological patient' characteristics and explored their possible predictive/prognostic role. We analyzed the expression of CD133 and ALDH enzymatic activity in 108 human ovarian cancer samples. We found that among the total patients analyzed, 13% of them was completely negative for ALDH activity and 26% was negative for CD133 staining. Both markers were variably expressed within the samples and when both studied in the same tumor sample, no statistically significant correlation between ALDH enzymatic activity and CD133 expression was found. No statistical significant correlation was found also between the percentage values of positive ALDH and CD133 cells and the number of serial passages patient's cultures underwent, suggesting that these markers do not confer by themselves a self-renewal growth advantage to the cultures. Lower levels of CD133 were associated with higher tumor grade. No correlation with response to therapy, progression free survival and overall survival was found. Our data suggest that neither ALDH enzymatic activity nor CD133 expression provide additional predictive/prognostic information in ovarian cancer patients.
    American Journal of Cancer Research 04/2013; 3(2):221-229. · 4.17 Impact Factor
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    • "In fibroblasts the gene PROM1 encoding the CD133 surface antigen was significantly down-regulated in comparison with small putative ovarian stem cells. CD133 is known to be expressed in different types of adult stem cells, such as hematopoietic stem cells [28] and in VSELs from human umbilical cord blood [10], and is related to the manifestation of different cancers, including ovarian cancer [29]. Primordial germ cell (PGC)-related genes PRDM1 (BLIMP1) and PRDM14 were strongly expressed in small putative ovarian stem cells. "
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    ABSTRACT: Background It has already been found that very small embyronic-like stem cells (VSELs) are present in adult human tissues and organs. The aim of this study was to find if there exists any similar population of cells in cell cultures of reproductive tissues and embryonic stem cells, and if these cells have any relation to pluripotency and germinal lineage. Methods and results Here we report that a population of small SSEA-4-positive cells with diameters of up to 4 μm was isolated by fluorescence-activated cell sorting (FACS) from the human ovarian cell cultures after enzymatic degradation of adult cortex tissues. These small cells – putative ovarian stem cells – were also observed during cell culturing of up to 6 months and more. In general, small putative ovarian stem cells, isolated by FACS, showed a relatively low gene expression profile when compared to human embryonic stem cells (hESCs) and human adult fibroblasts; this may reflect the quiescent state of these cells. In spite of that, small putative ovarian stem cells expressed several genes related to primordial germ cells (PGCs), pluripotency and germinal lineage, including VASA. The PGC-related gene PRDM1 was strongly expressed in small putative ovarian stem cells; in both hESCs and fibroblasts it was significantly down-regulated. In addition, putative ovarian stem cells expressed other PGC-related genes, such as PRDM14 and DPPA3. Most of the pluripotency and germinal lineage-related genes were up-regulated in hESCs (except VASA). When compared to fibroblasts, there were several pluripotency-related genes, which were up-regulated in small putative ovarian stem cells. Similar populations of small cells were also isolated by FACS from human testicular and hESC cultures. Conclusions Our results confirm the potential embryonic-like character of small putative stem cells isolated from human adult ovaries and their possible relation to germinal lineage.
    Journal of Ovarian Research 04/2013; 6(1):24. DOI:10.1186/1757-2215-6-24 · 2.43 Impact Factor
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