• Media type: E-Article
  • Title: Association of ERCC1 protein expression to platinum resistance in epithelial ovarian cancer
  • Contributor: Steffensen, K. D.; Waldstrøm, M.; Jakobsen, A.
  • imprint: American Society of Clinical Oncology (ASCO), 2009
  • Published in: Journal of Clinical Oncology
  • Language: English
  • DOI: 10.1200/jco.2009.27.15_suppl.5530
  • ISSN: 0732-183X; 1527-7755
  • Keywords: Cancer Research ; Oncology
  • Origination:
  • Footnote:
  • Description: <jats:p> 5530 </jats:p><jats:p> Background: Although platinum-based chemotherapy remains the cornerstone for treatment of ovarian cancer, some patients are resistant to the treatment and will therefore not benefit from the standard platinum-based chemotherapy. Preclinical and clinical data have suggested a potential use of ERCC1 (excision repair cross-complementation group 1 enzyme) as a molecular predictor of clinical resistance to platinum-based chemotherapy. ERCC1 is a key enzyme in the nucleotide excision repair pathway which is involved in the DNA repair mechanisms in tumor cells. The primary aim of the present study was to investigate if immunohistochemical expression of ERCC1 protein was associated with resistance to standard combination carboplatin and paclitaxel chemotherapy in newly diagnosed ovarian cancer patients. Methods: Formalin-fixed, paraffin-embedded tissue sections from 101 patients with newly diagnosed ovarian cancer were used for immunohistochemical staining for the ERCC1 protein. The percentage of positive tumor cells in each slide were scored as 0 if 0 % of the tumor cells were positive, 0.1 if 1 %-9 %; 0.5 if 10 %-49 %; and 1.0 if 50 % or more were positive. A semi quantitative H-score was calculated by multiplying the staining intensity (0–3) with the percentage score. The tumor was considered positive when the H-score was &gt; 1.0. All patients received carboplatin-paclitaxel combination chemotherapy. Results: ERCC1 protein overexpression was found in 13.9 % of the tumors. Platinum resistance were found in 75 % of the tumors with positive ERCC1 protein expression compared to 27 % among the patients with negative tumor staining for ERCC1 (p = 0.0013). These findings translated into a significant difference in progression free survival in both univariate (p = 0.0012) and in multivariate analysis (p = 0.006). Conclusions: The data presented suggests a positive association between positive ERCC1 protein expression and clinical resistance to platinum-based chemotherapy. </jats:p><jats:p> No significant financial relationships to disclose. </jats:p>
  • Access State: Open Access