Abstract
Background
Tumor-infiltrating lymphocytes influence the prognosis of solid tumors, including ovarian cancer (OC). The immunoregulatory transcription factor (IRF4) is mainly expressed in plasma cells and regulates immunoglobulin class switch recombination as well as plasma cell differentiation. Therefore, we analyzed the impact of IRF4 expression in a consecutive cohort of OC patients.
Methods
IRF4 expression was evaluated by immunostaining. Differences in IRF4 expression among the subgroups of the established clinical−pathological features like age, histological subtype, tumor stage, histological grading, postoperative tumor burden, and completeness of chemotherapy were determined by χ2 test. The impact of IRF4 expression on progression-free survival (PFS) and overall survival (OS) was examined by univariate and multivariate Cox analysis adjusted for established clinical−pathological factors and Kaplan–Meier survival analysis.
Results
114 patients entered this study. IRF4 was expressed in 51.7% of the entire cohort. 72.3% patients with high-grade serous OC showed IRF4 expression compared to 37.3% patients with a non-high-grade serous OC (p < 0.001). Univariate Cox-regression analysis revealed no prognostic impact of IRF4 expression in terms of PFS (p = 0.35) and OS (p = 0.98). Kaplan–Meier plots failed to show any prognostic impact for PFS (p = 0.35) and OS (p = 0.98), too. Established clinical–pathological factors retained their prognostic impact as tumor stage in terms of PFS (< 0.001) and as postoperative residual tumor burden (p = 0.04), tumor stage (< 0.001), histological grade (p = 0.02), and completeness of chemotherapy (p < 0.001) in terms of OS, respectively.
Conclusion
Immunohistochemically determined IRF4 expression correlated with high-grade serous OC. However, it failed to show any prognostic impact in this cohort of 114 patients.
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ASH: project development, data collection, immunostaining, statistical analysis, manuscript writing. MS: project development, manuscript editing, supervision. KA: data curation, support. JJ: evaluation of immunostaining, manuscript editing. SG: technical support, immunostaining. VWE: support statistical analysis. TE: methodology support. KK: formal analysis support. WB: protocol/project development, supervision. AH: project development, manuscript editing, supervision. MJB: data collection, protocol development, manuscript editing, supervision.
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The study was approved by the Research Ethics Committee of the University Medical Centre Mainz, Germany. Informed consent was obtained from all the patients, and all the clinical investigations were conducted according to the ethical and legal standards, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All the authors have approved the manuscript and agreed with the submission to Archives of Gynecology and Obstetrics.
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Heimes, AS., Schmidt, M., Jäkel, J. et al. A retrospective analysis of immunohistochemically determined IRF4 (interferon regulating factor 4) expression in a consecutive cohort of 114 ovarian cancer patients. Arch Gynecol Obstet 299, 239–246 (2019). https://doi.org/10.1007/s00404-018-4941-z
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DOI: https://doi.org/10.1007/s00404-018-4941-z