Abstract
Purpose: A crucial step in the DNA base excision repair pathway involves the cleavage of an apurinic/apyrimidinic site by an apurinic/apyrimidinic endonuclease (APE). The major APE in mammalian cells is APE/ref-1, a multifunctional enzyme that acts not only as a DNA repair enzyme but as a redox-modifying factor for a variety of transcription factors. The purpose of this study is to determine whether APE/ref-1 expression differs with ovarian cancer progression and metastasis and in platinum-resistant disease. Experimental Design: Ovarian tissue sections were obtained from the Cooperative Human Tissue Network for studies of APE/ref-1 expression and the metastatic process and from our institutional Department of Pathology for studies of APE/ref-1 expression and platinum resistance. Tissue microsections from formalin-fixed, paraffin-embedded specimens of epithelial ovarian cancers were stained using a monoclonal antibody to APE/ref-1 followed by standard immunohistochemical techniques. Slides were then analyzed for the percentage of positively staining nuclei as well as staining intensity using a blinded coding system. Results: All epithelial ovarian cancers expressed APE/ref-1. There were no significant differences in the percentage or intensity of nuclear staining in primary tumors from patients with early- versus advanced-stage disease or in primary tumors versus metastasis from patients with advanced disease. Both platinum-sensitive and platinum-refractory tumors demonstrated a range from minimal to high intensity staining nuclei with a median value of 2+ staining on a scale of 0-3+. The median value for the percentage of nuclei involved was 70% in the platinum-sensitive group and 90% in the platinum-refractory group (P = 0.118). Conclusions: APE/ref-1 expression is ubiquitous among epithelial ovarian cancers and is unaltered with the metastatic process. APE/ref-1 expression does not appear to differ between platinum-sensitive and platinum-refractory ovarian cancers and thus is not a useful biomarker for platinum resistance. Combined with evidence that APE/ref-1 expression and function may not be equivalent in all cell types and tissues, future work will investigate APE/ref-1 as a potential therapeutic target.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4689-4694 |
| Number of pages | 6 |
| Journal | Clinical Cancer Research |
| Volume | 9 |
| Issue number | 13 |
| State | Published - Oct 15 2003 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Studies of Apurinic/Apyrimidinic Endonuclease/ref-1 Expression in Epithelial Ovarian Cancer : Correlations with Tumor Progression and Platinum Resistance. / Freitas, Sarah; Moore, David H.; Michael, Helen; Kelley, Mark R.
In: Clinical Cancer Research, Vol. 9, No. 13, 15.10.2003, p. 4689-4694.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Studies of Apurinic/Apyrimidinic Endonuclease/ref-1 Expression in Epithelial Ovarian Cancer
T2 - Correlations with Tumor Progression and Platinum Resistance
AU - Freitas, Sarah
AU - Moore, David H.
AU - Michael, Helen
AU - Kelley, Mark R.
PY - 2003/10/15
Y1 - 2003/10/15
N2 - Purpose: A crucial step in the DNA base excision repair pathway involves the cleavage of an apurinic/apyrimidinic site by an apurinic/apyrimidinic endonuclease (APE). The major APE in mammalian cells is APE/ref-1, a multifunctional enzyme that acts not only as a DNA repair enzyme but as a redox-modifying factor for a variety of transcription factors. The purpose of this study is to determine whether APE/ref-1 expression differs with ovarian cancer progression and metastasis and in platinum-resistant disease. Experimental Design: Ovarian tissue sections were obtained from the Cooperative Human Tissue Network for studies of APE/ref-1 expression and the metastatic process and from our institutional Department of Pathology for studies of APE/ref-1 expression and platinum resistance. Tissue microsections from formalin-fixed, paraffin-embedded specimens of epithelial ovarian cancers were stained using a monoclonal antibody to APE/ref-1 followed by standard immunohistochemical techniques. Slides were then analyzed for the percentage of positively staining nuclei as well as staining intensity using a blinded coding system. Results: All epithelial ovarian cancers expressed APE/ref-1. There were no significant differences in the percentage or intensity of nuclear staining in primary tumors from patients with early- versus advanced-stage disease or in primary tumors versus metastasis from patients with advanced disease. Both platinum-sensitive and platinum-refractory tumors demonstrated a range from minimal to high intensity staining nuclei with a median value of 2+ staining on a scale of 0-3+. The median value for the percentage of nuclei involved was 70% in the platinum-sensitive group and 90% in the platinum-refractory group (P = 0.118). Conclusions: APE/ref-1 expression is ubiquitous among epithelial ovarian cancers and is unaltered with the metastatic process. APE/ref-1 expression does not appear to differ between platinum-sensitive and platinum-refractory ovarian cancers and thus is not a useful biomarker for platinum resistance. Combined with evidence that APE/ref-1 expression and function may not be equivalent in all cell types and tissues, future work will investigate APE/ref-1 as a potential therapeutic target.
AB - Purpose: A crucial step in the DNA base excision repair pathway involves the cleavage of an apurinic/apyrimidinic site by an apurinic/apyrimidinic endonuclease (APE). The major APE in mammalian cells is APE/ref-1, a multifunctional enzyme that acts not only as a DNA repair enzyme but as a redox-modifying factor for a variety of transcription factors. The purpose of this study is to determine whether APE/ref-1 expression differs with ovarian cancer progression and metastasis and in platinum-resistant disease. Experimental Design: Ovarian tissue sections were obtained from the Cooperative Human Tissue Network for studies of APE/ref-1 expression and the metastatic process and from our institutional Department of Pathology for studies of APE/ref-1 expression and platinum resistance. Tissue microsections from formalin-fixed, paraffin-embedded specimens of epithelial ovarian cancers were stained using a monoclonal antibody to APE/ref-1 followed by standard immunohistochemical techniques. Slides were then analyzed for the percentage of positively staining nuclei as well as staining intensity using a blinded coding system. Results: All epithelial ovarian cancers expressed APE/ref-1. There were no significant differences in the percentage or intensity of nuclear staining in primary tumors from patients with early- versus advanced-stage disease or in primary tumors versus metastasis from patients with advanced disease. Both platinum-sensitive and platinum-refractory tumors demonstrated a range from minimal to high intensity staining nuclei with a median value of 2+ staining on a scale of 0-3+. The median value for the percentage of nuclei involved was 70% in the platinum-sensitive group and 90% in the platinum-refractory group (P = 0.118). Conclusions: APE/ref-1 expression is ubiquitous among epithelial ovarian cancers and is unaltered with the metastatic process. APE/ref-1 expression does not appear to differ between platinum-sensitive and platinum-refractory ovarian cancers and thus is not a useful biomarker for platinum resistance. Combined with evidence that APE/ref-1 expression and function may not be equivalent in all cell types and tissues, future work will investigate APE/ref-1 as a potential therapeutic target.
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M3 - Article
C2 - 14581338
AN - SCOPUS:0142219356
VL - 9
SP - 4689
EP - 4694
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 13
ER -