ABSTRACT
Tumors harboring homologous recombination deficiency (HRD) are considered optimal candidates for poly(ADP-ribose) polymerase 1 (PARP) inhibitor treatment. Such deficiency can be detected by analyzing breast cancer type (BRCA)1/2 gene mutations, as well as mutations in other genes of the homologous recombination pathway. The algorithmic measurement of the HRD effect by identifying genomic instability (GI) has been used as biomarker. As compared with the direct measurement of somatic gene alterations, this approach increases the number of patients who could benefit from PARP inhibitor treatment. In the present study, the performance of the Oncoscan CNV assay, accompanied by appropriate bioinformatic algorithms, was evaluated for its performance in GI calculation and was compared with that of a validated next-generation sequencing (NGS) test (myChoice HRD test). In addition, the clinical utility of the GI score (GIS) and BRCA1/2 tumor analysis were investigated in a cohort of 444 patients with ovarian cancer. For that reason, single nucleotide polymorphism (SNP) arrays and appropriate bioinformatics algorithms were used to calculate GIS in 29 patients with ovarian cancer with known GIS status using a validated NGS test. Furthermore, BRCA1/2 analysis results were compared between the aforementioned assay and the amplicon-based Oncomine™ BRCA Research Assay. BRCA1/2 analysis was performed in 444 patients with ovarian cancer, while GIS was calculated in 175 BRCA1/2-negative cases. The bioinformatics algorithm developed for GIS calculation in combination with NGS BRCA1/2 analysis (RediScore), and the OncoscanR pipeline exhibited a high overall agreement with the validated test (93.1%). In addition, the Oncomine NGS assay had a 100% agreement with the validated test. The BRCA1/2 mutation frequency was 26.5% in the examined patients with ovarian cancer. GIS was positive in 40% of the BRCA1/2-negative cases. The RediScore bioinformatics algorithm developed for GIS calculation in combination with NGS BRCA1/2 analysis is a viable and effective approach for HRD calculation in patients with ovarian cancer, offering a positive prediction for PARP inhibitor responsiveness in 55% of the patients.
ABSTRACT
BACKGROUND: Interleukin-6 (IL-6) has been implicated in various malignancies, including ovarian cancer. However, mixed results have been observed regarding IL-6 levels in different ovarian conditions. This meta-analysis was performed to determine IL-6 levels in the peritoneal fluid and peripheral blood among patients with various adnexal masses. METHODS: Most popular English databases were searched using a predefined search formula. All studies comparing IL-6 levels in plasma, serum or peritoneal fluid of patients with benign tumors, ovarian neoplasms, and healthy controls were included based on inclusion and exclusion criteria. RESULTS: 5953 patients from 22 primary publications raging from 1994 to 2021 were included in the meta-analyses. A pooled IL-6 Mean Difference (MD) of 41 pg/mL for malignant tumors compared to benign ones, with a Confidence Interval (CI) between 19.8 and 62.2, a Z-score of 3.79, and statistical significance with a p = 0.0002 was observed. Pooled results for healthy versus benign ovarian conditions showed an MD of 5.45 pg/mL for serum or plasma IL-6 measurements in favor of benign tumors (CI:0.66-10.25, Z = 2.23 and p = 0.03). The analysis showed an MD for IL-6 levels of 19.59 pg/mL for healthy controls versus malignant ovarian tumors. Peritoneal fluid measurements regarding IL-6's levels showed no significant difference between benign or malignant masses. DISCUSSION/CONCLUSIONS: Higher levels of plasma or serum IL-6 in ovarian neoplasia patients compared to benign conditions or healthy controls identify IL-6 as a discerning factor between benign or malignant ovarian tumors and a potential biomarker for ovarian malignancy.
Subject(s)
Interleukin-6 , Ovarian Neoplasms , Female , Humans , Ovarian Neoplasms/pathology , Ascitic Fluid/chemistry , Ascitic Fluid/pathology , BiomarkersABSTRACT
PURPOSE: Tumor infiltrating lymphocytes (TILs) in cutaneous malignant melanoma are classified as brisk, non-brisk or absent. Numerous studies suggest the presence of TILs, especially brisk, are associated with a lower rate of lymph node metastasis and with an improved overall survival (OS). Our purpose was to assess the value of TILs as a prognostic factor for the lymph node metastasis and survival in completely resected pT3 stage malignant melanoma patients. METHODS: We included a number of 114 patients with pathological pT3 cutaneous malignant melanoma, treated exclusively in our institution, between 2000-2015. Correlations of clinical and pathological factors with lymph node status and OS were analyzed. RESULTS: A brisk infiltrate was present in 60% of the patients, whereas 40% presented a non-brisk infiltrate or absent TILs. In univariate analysis, the presence of ulceration was correlated with a non-brisk infiltrate, whereas in multivariate analysis, lymph node invasion and a non-brisk infiltrate were associated with a higher risk of death. CONCLUSIONS: TILs density grade represents an independent prognostic factor for the OS. Therefore, we conclude that an accurate prognosis may be provided by TILs status in patients with pT3 malignant melanoma.
