Nibrin is a marker of clinical outcome in patients with advanced serous ovarian cancer treated in the phase III OVA-301 trial

作者：Monk Bradley J; Kaye Stanley B; Poveda Andres; Herzog Thomas J; Aracil Miguel; Nieto Antonio; Badri Nadia; Parekh Trilok V; Tanovic Adnan; Galmarini Carlos M^*

来源：Gynecologic Oncology, 2014, 132(1): 176-180.

DOI：10.1016/j.ygyno.2013.10.032

• Trabectedin
• Nibrin
• Ovarian cancer
• Molecular marker

Objective. This study investigated the relationship between 13 proteins involved in DNA damage and the outcomes of patients with recurrent ovarian cancer (ROC). %26lt;br%26gt;Patients and methods. Immunohistochemistry staining was performed in 114 diagnostic samples from patients with serous ROC who participated in the OVA-301 study, which compared pegylated liposomal doxorubicin (PLD) with a combination of trabectedin plus PLD. Percentage of positive cells for every marker was calculated and correlated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). %26lt;br%26gt;Results. A statistically significant correlation between high levels of nibrin and lower ORR (P = 0.03), shorter PFS (P = 0.007) and shorter OS (P = 0.01) was observed. After stratification, in patients with platinum-sensitive disease treated with the combination of trabectedin plus PLD, high levels of nibrin correlated with lower ORR (P = 0.01) and shorter PFS (P = 0.02). A better clinical outcome (ORR, PFS and OS) was also associated to low levels of CHK2 in trabectedin plus PLD treated patients. No correlations were found in PLD-treated patients. According to the results of a multivariate analysis, there was a statistically significant correlation between high nibrin (P = 0.001) and low BRCA2 levels (P = 0.03) and a worse PFS, and between high nibrin levels and a worse OS (P = 0.006). %26lt;br%26gt;Conclusion. Our results indicate that high nibrin expression seems to be associated with a worse clinical outcome in serous ROC, particularly in patients treated with the combination trabectedin plus PLO. Prospective studies to determine clinical usefulness of nibrin as a possible biornarker in other series of patients with ROC are warranted.

• 出版日期2014-1