Background
The consequences of defective homologous recombination (HR) are not understood in
sporadic ovarian cancer, nor have the potential role of HR proteins other than BRCA1 and BRCA2 been clearly defined. However, it is clear that defects in HR and other DNA repair pathways are important to the effectiveness of current therapies. We hypothesize that a subset of sporadic ovarian carcinomas may harbor anomalies in HR pathways, and that a
BRCAness profile (defects in HR or other DNA repair pathways) could influence response rate and survival after treatment with platinum drugs. Clinical availability of a BRCAness profile in patients and/or tumors should improve treatment outcomes.
Objective
To define the BRCAness profile of sporadic ovarian carcinoma and determine whether BRCA1, PARP, FANCD2, PTEN, H2AX, ATM, and P53 protein expression correlates with response to treatment, disease recurrence, and recurrence-free survival.
Results
High
PARP, FANCD2 and BRCA1 expressions were significantly correlated with
each other; however, elevated p53 expression was associated only with
high PARP and FANCD2. Of all patients, 9% recurred within the first
year. Among early recurring patients, 41% had high levels of PARP,
FANCD2 and P53, compared to 19.5% of patients without early recurrence
(p = 0.04). Women with high levels of PARP, FANCD2 and/or P53 had first
year cumulative cancer incidence of 17% compared with 7% for the other
groups (P = 0.03).
Conclusions
Patients
with concomitantly high levels of PARP, FANCD2 and P53 protein
expression are at increased risk of early ovarian cancer recurrence and
platinum resistance.
