Abstract
(1) Background: The mechanism of platinum resistance in ovarian cancer is not fully clarified, but the properly functioning DNA repair mechanism can counteract the effect of conventional anticancer treatment. The objective of our study was to evaluate the expression of an important DNA repair enzyme, the Poly (ADP-Ribose) Polymerase (PARP) expression in epithelial ovarian cancer (EOC) tissues depending on BRCA status and to assess its relationship with platinum resistance. (2) Methods: Immunostaining to highlight PARP protein expression was performed using a rabbit polyclonal anti-PARP antibody. The intensity and distribution of immunostaining were assessed by light. Somatic BRCA1 or BRCA2 mutation carriers were identified with bidirectional sequencing of DNA from archived tumor tissue, if the test could not be performed due to technical reasons from tumor cells, the sequencing was done from peripheral blood cells to identify germline mutation carriers. 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. (3) Results: In the overall population, negative PARP immunohistochemistry predicted significant PFS (20.1 vs. 11.9 months, p = 0.001) and OS (49 vs. 114 months, p = 0.014) benefit. Genotype-stratified subgroup analysis in BRCA-negative cases confirmed the role of PARP positivity indicating an unfavorable prognosis in the entire population (relapsed 73.91% vs. 92%; OR: 4.06; p = 0.04). In the cases of the subgroup carrying the BRCA mutation, the presence of PARP expression was not associated with less favorable relapse rates, but with marginal significance for overall survival predicted a lower chance of survival (OS more than 32 months 72.73% vs. 35%; OR: 0.2; p = 0.05). (4) Conclusion: The BRCA wild type patients with strong expression of PARP enzymes before the first set of chemotherapy have a poor prognosis.
Highlights
Ovarian cancer is one of the most common gynecological malignancies [1,2]
In the cases of the subgroup carrying the BRCA mutation, the presence of Poly (ADP-Ribose) Polymerase (PARP) expression was not associated with less favorable relapse rates, but with marginal significance for overall survival predicted a lower chance of survival (OS more than 32 months 72.73% vs. 35%; odds ratio (OR): 0.2; p = 0.05)
The main aim of our study is to evaluate PARP expression in epithelial ovarian cancer (EOC) tissues depending on BRCA status and assess its relationship with platinum resistance
Summary
Ovarian cancer is one of the most common gynecological malignancies [1,2]. The standard therapy stands from debulking surgery and platinum-based chemotherapy [4]. We currently consider the success of debulking surgery and the response to platinum-based chemotherapy to be the most important prognostic factors for disease outcome [3,5]. The carcinogenesis of ovarian cancer is not fully clarified, but to other tumors, the accumulation of DNA damage and alterations in genome maintenance has an important role [6]. The genome stability is controlled by several DNA repair mechanisms, damage tolerance, and checkpoint pathways, counteracting the harmful effects [6]. DNA remains highly vulnerable, any faulty repair or replication can lead to further mutations, loss of tumor suppressor genes, or activation of oncogenes, thereby causing uncontrolled cell proliferation [6]
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