Expression of steroid receptor coactivator 3 in ovarian epithelial cancer is a poor prognostic factor and a marker for platinum resistance
A partir de l'analyse immunohistochimique d'échantillons tumoraux prélevés sur 471 patientes atteintes d'un cancer épithélial de l'ovaire traité entre 1991 et 2006 par cytoréduction chirurgicale et chimiothérapie de première ligne combinant ou non sels de platine et taxane, cette étude montre que l'expression tumorale du co-activateur 3 des récepteurs aux hormones stéroïdiennes est associé à un pronostic défavorable et à la résistance aux sels de platine
Background : Steroid receptor coactivator 3 (SRC3) is an important coactivator of a number of transcription factors and is associated with a poor outcome in numerous tumours. Steroid receptor coactivator 3 is amplified in 25% of epithelial ovarian cancers (EOCs) and its expression is higher in EOCs compared with non-malignant tissue. No data is currently available with regard to the expression of SRC-3 in EOC and its influence on outcome or the efficacy of treatment.
Methods : Immunohistochemistry was performed for SRC3, oestrogen receptor-
α, HER2, PAX2 and PAR6, and protein expression was quantified using automated quantitative immunofluorescence (AQUA) in 471 EOCs treated between 1991 and 2006 with cytoreductive surgery followed by first-line treatment platinum-based therapy, with or without a taxane.
Results
:
Steroid receptor coactivator 3 expression was significantly associated with advanced stage and was an independent prognostic marker. High expression of SRC3 identified patients who have a significantly poorer survival with single-agent carboplatin chemotherapy, while with carboplatin/paclitaxel treatment such a difference was not seen.
Conclusion
:
Steroid receptor coactivator 3 is a poor prognostic factor in EOCs and appears to identify a population of patients who would benefit from the addition of taxanes to their chemotherapy regimen, due to intrinsic resistance to platinum therapy.
British Journal of Cancer , résumé, 2012