Abstract
In an attempt to clarify the prognostic relevance of poly (ADP-ribose) polymerase (PARP) expression, we analysed the clinical data of 86 high-grade epithelial ovarian cancer (EOC) cases in which PARP immunohistochemistry results were available. Immunostaining to highlight PARP protein expression was performed using a Leica Bond MAX Immunostainer (Leica Microsystems, Wetzlar, Germany). We applied a rabbit polyclonal anti-PARP antibody (ab6079 330, Abcam, Cambridge, UK) for the specific reaction. The intensity and distribution of immunostaining were assessed by light microscopy (Leica DM2500 microscope, DFC 420 camera, and Leica Application Suite V3 software; Leica) and evaluated with a four-grade (0–3+) system. The median progression-free survival (PFS) was generated for each semiquantitative group of PARP expression among chemotherapy-naive cases at the time of PARP immunohistochemistry. Eighty-six cases were chemotherapy-naive at the time of PARP immunohistochemistry, and 41 cases showed no PARP expression. Forty-five cases showed intermediate or high PARP expression. The median PFS among patients in the PARP-negative group was 16 months (interquartile range; IQR 10.7–35.9 months), and the median PFS of patients in the PARP-positive group was 12 months (IQR 6.1–21.8 months). The difference was significant according to the log-rank test (p = 0.01). The median overall survival (OS) of patients in the PARP-negative group was 65 months (IQR 43.6–110.8 months), and the median OS of patients in the PARP-positive group was 52 months (IQR 36.9–66.7 months). The difference was significant according to the log-rank test (p = 0.028). Multiple comparisons confirmed that PARP expression results in a significant difference in PFS and OS achieved by first-line Taxol-carboplatin chemotherapy. The lack of PARP expression assessed by immunohistochemistry may predict improved PFS in ovarian cancer patients after adjuvant platinum-based chemotherapy.
Highlights
Ovarian cancer has the highest mortality among female genital cancers, and it is the seventh most significant contributor to cancer mortality [1, 2]
In an attempt to clarify the prognostic relevance of Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) expression, we analysed clinical data of high-grade Epithelial ovarian cancer (EOC) cases in which PARP immunohistochemistry results were available
Zhang et al uncovered a molecular mechanism by which BRCA2 participates in DNA damage repair
Summary
Ovarian cancer has the highest mortality among female genital cancers, and it is the seventh most significant contributor to cancer mortality [1, 2]. Immunohistochemical staining for the p53 protein is positive in a significant proportion of these lesions, similar to highgrade serous ovarian cancer [4, 5]. The effect of conventional anticancer therapies is damage to nuclear DNA and chromosomal integrity. These treatments primarily destroy cancer cells and reduce their survival capacity. Adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibition is one of the latest therapeutic approaches for the treatment of ovarian cancer. BRCA mutations are one of the most common hereditary genetic defects that occur in ovarian cancer. In the presence of homologous recombination repair deficiency, PARP inhibition causes unrepaired DNA damage in tumour cells. PARP expression may be a marker of decreased sensitivity to DNA-damaging environmental effects, such as platinumbased chemotherapy
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