Abstract
Objective
Approximately
20% of patients receiving platinum-based chemotherapy for epithelial
ovarian cancer (EOC) are refractory or develop early recurrence.
Identifying these patients early could reduce treatment-associated
morbidity and allow quicker transfer to more effective therapies. Much
attention has focused on ERCC1 as a potential predictor of response to
therapy because of its essential role in the repair of platinum-induced
DNA damage. The purpose of this study was to accurately measure protein
levels of ERCC1 and its essential binding partner XPF from patients with
EOC treated with platinum-based therapy and determine if protein levels
correlate with mRNA levels, patient genotypes or clinical outcomes.
Methods
ERCC1 and XPF
mRNA and protein levels were measured in frozen EOC specimens from 41
patients receiving intraperitoneal platinum-based chemotherapy using
reverse transcription polymerase chain reaction and western blots.
Genotypes of common nucleotide polymorphisms were also analyzed. Patient
outcomes included progression free (PFS) and overall survival (OS).
Results
Expression of ERCC1 and XPF
were tightly correlated with one another at both the mRNA and protein
level. However, the mRNA and protein levels of ERCC1 were not positively
correlated. Likewise, none of the SNPs analyzed correlated with ERCC1
or XPF protein levels. There was an inverse correlation between mRNA
levels and patient outcomes.
Conclusion
Neither genotype nor mRNA levels are predictive of protein expression. Despite this, low ERCC1 mRNA significantly correlated with improved PFS and OS.
