High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma.

BACKGROUND: Mechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of protein expression of EVI1 alone and in combination with PARP1 and analyzed them in a cohort of patients with HGSOC. METHODS: For 562 HGSOC patients, we evaluated EVI1 and PARP1 expression by immunohistochemical staining on tissue microarrays with QuPath digital semi-automatic positive cell detection. RESULTS: High EVI1 expressing (> 30% positive tumor cells) HGSOC were associated with improved progression-free survival (PFS) (HR = 0.66, 95% CI: 0.504-0.852, p = 0.002) and overall survival (OS) (HR = 0.45, 95% CI: 0.352-0.563, p < 0.001), including multivariate analysis. Most interestingly, mutual high expression of both proteins identifies a group with particularly good prognosis. Our findings were proven technically and clinically using bioinformatical data sets for single-cell sequencing, copy number variation and gene as well as protein expression. CONCLUSIONS: EVI1 and PARP1 are robust prognostic biomarkers for favorable prognosis in HGSOC and imply further research with respect to their reciprocity.

Increased expression of IDO1 is associated with improved survival and increased number of TILs in patients with high-grade serous ovarian cancer.

BACKGROUND: The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) plays a crucial role in regulating the immune system's response to tumors, but its exact role in cancer, especially in high-grade serous ovarian cancer (HGSOC), remains controversial. We aimed to investigate the prognostic impact of IDO1 expression and its correlation with tumor-infiltrating lymphocytes (TILs) in HGSOC. METHODS: Immunohistochemical (IHC) staining and bioimage analysis using the QuPath software were employed to assess IDO1 protein expression in a well-characterized cohort of 507 patients with primary HGSOC. Statistical evaluation was performed using SPSS, and in silico validation considering IDO1 mRNA expression in bulk and single-cell gene expression datasets was conducted. Additionally, IDO1 expression in interferon-gamma (IFNG) stimulated HGSOC cell lines was analyzed. RESULTS: Our findings revealed that IDO1 protein and mRNA expression serve as positive prognostic markers for overall survival (OS) and progression-free survival (PFS) in HGSOC. High IDO1 expression was associated with a significant improvement in OS by 21 months (p < 0.001) and PFS by 6 months (p = 0.016). Notably, elevated IDO1 expression correlated with an increased number of CD3+ (p < 0.001), CD4+ (p < 0.001), and CD8+ TILs (p < 0.001). Furthermore, high IDO1 mRNA expression and protein level were found to be associated with enhanced responsiveness to pro-inflammatory cytokines, particularly IFNG. CONCLUSIONS: Our study provides evidence that IDO1 expression serves as a positive prognostic marker in HGSOC and is associated with an increased number of CD3+, CD4+ and CD8+ TILs. Understanding the intricate relationship between IDO1, TILs, and the tumor microenvironment may hold the key to improving outcomes in HGSOC.

Clinical outcome of tertiary surgical cytoreduction in patients with recurrent epithelial ovarian cancer.

BACKGROUND: The value of tertiary cytoreductive surgery (TCS) on overall survival (OS) of patients with relapsed epithelial ovarian cancer (ROC) is not well defined. Aim of the present study was to evaluate the operative and clinical outcome after TCS. METHODS: We systematically evaluated all consecutive patients undergoing TCS. Tumor dissemination pattern, operative morbidity, residual tumor, and survival are described based on a validated intraoperative documentation tool. Predictors of survival and complete tumor resection are analyzed with Cox regression or logistic regression models. RESULTS: Between October 2000 and December 2008, 135 patients (median age, 51 years; range, 22-80 years) of mainly initial FIGO stage ≥ III (106 patients, 78.5%) were evaluated. In 53 patients (39.3%) a complete tumor-resection was obtained. The 1-month operative mortality was 6%. During a median follow-up period of 9.6 months (range, 0.1-75 months), 78 patients (57.8%) died, while 52 patients (38.5%) experienced a further relapse. Median OS was 19.1 months for the total collective (95% confidence interval [95% CI], 14.84-23.35). Median OS was 37.8 months (95% CI, 12.7-62.7) for patients without residual tumor; versus 19.0 months (95% CI, 9.8-28.2) for residual tumor ≤ 1 cm and 6.9 months (95% CI, 3.05-10.7) for residual tumor > 1 cm (P < .001). The presence of peritoneal carcinomatosis did not seem to significantly affect OS. Complete tumor resection was identified as the strongest predictor of OS. Other independent predictors of OS were interval to primary diagnosis ≥ 3 years (hazard ratio [HR], 0.28; 95% CI, 0.14-0.59) and serous papillary histology (HR, 0.23; 95% CI, 0.09-0.56). A total of 42 patients (31.1%) presented at least 1 major complication. Multivariate analysis identified tumor involvement of the middle abdomen and peritoneal carcinomatosis as independent predictors of complete tumor resection. CONCLUSIONS: Postoperative tumor residual disease remains the strongest predictor of survival even in TCS setting. To identify the optimal candidates for TCS, the predictive value of ascites and peritoneal carcinomatosis should be confirmed by future prospective trials.

CT-guided high-dose-rate brachytherapy of metachronous ovarian cancer metastasis to the liver: initial experience.

AIM: Hepatic resection for hepatic ovarian cancer metastases remains controversial. The purpose of this study was to evaluate the clinical outcome of CT-guided high dose rate brachytherapy (CT-HDRBT) for minimally invasive cytoreduction of isolated metachronous ovarian cancer metastases to the liver. PATIENTS AND METHODS: Seven patients with 12 isolated ovarian cancer metastases to the liver were treated with CT-HDRBT. To evaluate tumor response a gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced liver MRI was performed before, six weeks after and every third month after treatment. RESULTS: The mean MRI-follow-up period was 15.4 months. Tumors ranged from 13 to 120 mm in diameter. Complete ablation was achieved for all lesions. No complications occurred. No local progression was observed in any of the included patients. Overall survival was 100% after 12 months. Two patients died after 14 and 25 months, respectively. CONCLUSION: CT-HDRBT is a safe and valid technique for performing minimally invasive cytoreduction of metachronous isolated liver metastases from ovarian cancer.