Expression of DNA repair genes as biomarkers of outcome in Epithelial Ovarian Cancer: a GEICO study. Andres Poveda1, Antonio Casado2, Andres Cervantes3, Miquel Tarón4, Ignacio Romero1, Isabel Bover5, Antonio González Martín6, Ana Oaknin7, Belen Ojeda8, Jose Antonio Lopez Guerrero1.
1Fundación Instituto Valenciano de Oncología, Valencia; 2Hospital Clínico San Carlos, Madrid; 3Hospital Clínico, INCLIVA, University of Valencia; 4Lab. Pangaea Biotech, Barcelona; 5Hospital Son Llatzer, Mallorca;
Expression of DNA repair genes as biomarkers of outcome in Epithelial Ovarian Cancer: a GEICO study. Andres Poveda1, Antonio Casado2, Andres Cervantes3, Miquel Tarón4, Ignacio Romero1, Isabel Bover5, Antonio González Martín6, Ana Oaknin7, Belen Ojeda8, Jose Antonio Lopez Guerrero1.
1Fundación Instituto Valenciano de Oncología, Valencia; 2Hospital Clínico San Carlos, Madrid; 3Hospital Clínico, INCLIVA, University of Valencia; 4Lab. Pangaea Biotech, Barcelona; 5Hospital Son Llatzer, Mallorca; 6Hospital MD Anderson ,Madrid; 7Hospital Vall Hebrón, Barcelona; 8Hospital Sant Pau, Barcelona. SPAIN
BACKGROUND
The treatment of ovarian cancer (OC) is hindered by intrinsic or acquired resistance to platinum-based chemotherapy.
Breast cancer 1 (BRCA1), ERCC1 and XPG genes play a crucial role in DNA repair (Figure-1)
Their expression levels have been associated with response to platinum based chemotherapy (Quinn JE. Clin Cancer Res. 2007;13(24):7413-20. Saldivar JS. Gynecol Oncol. 2007;107(Suppl 1):S56-71.) (Figure-2)
Figure 1: Nucleotide excision repair pathway.
STUDY DESIGN
Paraffin-blocks of a series of 134 OC from women included in the GEICO-0101/OV-16 study were analyzed (Figure-3). One-hundred sixteen (86%) were valuable for the analysis.
All samples were laser captured micro-dissected.
The expression of BRCA1, ERCC1 and XPG genes was retrospectively evaluated in tumoral cells by qRT-PCR (Pangaea Biotech Lab).
The median values of expression were used as cut-off to separate high versus low expression patients.
The Fisher-Exact and Log-Rank tests were used for statistical analysis.
RESULTS
In global, low BRCA1 expression showed a not significative trend to higher overall survival (OS) (p=0.17), mainly in A1 (p=0.088) (Figure-4 and Figure-5).
Non-serous histology was associated to a worse DFS (p=0.009).
High XPG expression seemed to be associated with a better outcome in A2 (p=0.0559) (Figure-6), meanwhile in A1 the trend was in the opposite direction (Figure-7). ERCC1 low expression showed better DFS in both treatment arms, although it was not sta
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