Search

Objective: To evaluate the clinicopathological characteristics of primary mucinous ovarian carcinoma (MOC) and define oncologic outcomes. Material and Methods: This retrospective study reviewed patients diagnosed with primary MOC at a single institution and underwent primary treatment between 1990 and 2019. The clinicopathological factors affecting oncological outcomes and treatment response were evaluated. The Kaplan-Meier method was used to evaluate survival outcomes. Survival curves were compared using the log-rank test. Results: The cohort's (n=92) median (range) age was 48 (15-82) years. Seventy-five (81.5%) patients were in the International Federation of Gynecology and Obstetrics stage I-II. Forty patients received platinum-based adjuvant chemotherapy. The 5-year progression-free survival was 98% in stage I-II and 17% for stage III-IV (p<0.001). In multivariate analysis, the only independent risk factor for disease failure was stage (hazard ratio: 6.838, 95% confidence interval: 1,358-34,415; p=0.020). Conclusion: Advanced stage was an independent poor prognostic factor for recurrence in patient with MOC. [ABSTRACT FROM AUTHOR]

Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients. We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration. Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates. In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies. • High stage compared to low stage MOC have features suggestive of a more immunosuppressive environment. • High epithelial FOXP3+ T-regulatory cells associated with poorer overall survival, possibly inhibiting the immune response. • Most mucinous ovarian carcinomas are immunogenically 'cold' and tailored immune therapy approaches would be required. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to evaluate evolution and prognosis of mucinous ovarian carcinomas (mOC), with respect to the two invasive patterns: expansile and infiltrative invasion. Methods: This was a descriptive, retrospective, multicenter study conducted in 13 French centres from 1 January 2001 to 31 December 2019. All patients operated on for epithelial ovarian neoplasia of the mucinous type (infiltrative/expansile) were included, whether the surgery was performed immediately or after neoadjuvant chemotherapy. Results: A total of 94 women with mucinous carcinomas were included in the present study. Mucinous tumours were divided into 35 expansile (37%) and 59 infiltrative (63%) mOC. There was a statistically significant difference in early and late stages at initial diagnosis between expansile and infiltrative mOC. None of the expansile mOC showed metastatic lymph nodes, whereas almost a quarter of the infiltrative mOC were metastatic to the pelvic/para-aortic region. There was a clear difference in RFS, in favour of expansile mOC, with 90% survival at 5 years, compared with 60% for infiltrative mOC. Conclusions: Although infiltrative and expansile mOC belong to the same histological family, they present many distinctions in clinical presentation, histological invasion, and disease course. [ABSTRACT FROM AUTHOR]

Background: The proportion of women with mucinous ovarian carcinoma in whom nodal metastases are identified during staging remains unclear.Objectives: To review the literature on surgical lymph node assessment during staging of women diagnosed with mucinous ovarian carcinoma.Search Strategy: A systematic search using synonyms of 'mucinous ovarian carcinoma' and 'lymph node assessment' was conducted in PubMed, Scopus, Embase and the Cochrane Library.Selection Criteria: When they covered ten or more mucinous ovarian carcinoma cases, staging surgery and minimally one of the following outcomes: prevalence of metastases, stage shift or survival data.Data Collection and Analysis: Studies were quality evaluated with the Cochrane risk-of-bias assessment tool for non-randomised studies of interventions. Outcomes were pooled using an inverse variance weighted random effects model.Main Results: Sixteen studies were included. In 278 women with mucinous ovarian cancer suspected to be stage I-II, a pooled proportion of 0.8% (95% CI <0.1-2.9%) had lymph node metastases and were upstaged. In those suspected of stage I (n = 184), this proportion was 0.7% (95% CI <0.1-3.8%). No difference (P = 0.287) was found in metastases between sampling at 0.0% (95% CI 0.0-3.3%) and complete pelvic and/or para-aortic lymph node dissection at 1.2% (95% CI <0.1-4.2%). One study directly compared the survival of patients staged with and without lymph node dissection and reported no significant difference.Conclusions: Surgical lymph node assessment in women suspected of stage I-II mucinous ovarian carcinoma rarely identifies nodal metastases and consequently has no significant impact on staging.Tweetable Abstract: Surgical lymph node assessment in women with stage I-II mucinous ovarian cancer rarely has staging consequences. [ABSTRACT FROM AUTHOR]

Objective: The use of lymph node sampling during staging procedures in clinical early-stage mucinous ovarian carcinoma (MOC) is an ongoing matter of debate. Furthermore, the incidence of lymph node metastases (LNM) in MOC in relation to tumour grade (G) is unknown. We aimed to determine the incidence of LNM in clinical early-stage MOC per tumour grade.Design: Retrospective study with data from the Dutch Pathology Registry (PALGA).Setting: The Netherlands, 2002-2012.Population or Sample: Patients with MOC.Methods: Histology reports on patients with MOC diagnosed in the Netherlands between 2002 and 2012 were obtained from PALGA. Reports were reviewed for diagnosis, tumour grade and presence of LNM. Clinical data, surgery reports and radiology reports of patients with LNM were retrieved from hospital files.Main Outcome Measures: Incidence of LNM, disease-free survival (DFS).Results: Of 915 patients with MOC, 426 underwent lymph node sampling. Cytoreductive surgery was performed in 267 patients. The other 222 patients received staging without lymph node sampling. In eight of 426 patients, LNM were discovered by sampling. In four of 190 (2.1%) patients with G1 MOC, LNM were present, compared with one of 115 (0.9%) patients with G2 MOC and three of 22 (13.6%) patients with G3 MOC. Tumour grade was not specified in 99 patients. Patients with clinical early-stage MOC had no DFS benefit from lymph node sampling.Conclusions: LNM are rare in early-stage G1 and G2 MOC without clinical suspicion of LNM. Therefore, lymph node sampling can be omitted in these patients.Tweetable Abstract: Lymph node sampling can be omitted in clinical early-stage G1 and G2 mucinous ovarian cancer. [ABSTRACT FROM AUTHOR]

Mucinous epithelial ovarian cancer (mEOC) is a rare subset of epithelial ovarian cancer. When diagnosed at a late stage, its prognosis is very poor, as it is quite chemo-resistant. To find new therapeutic options for mEOC, we performed high-throughput screening using a siRNA library directed against human protein kinases in a mEOC cell line, and polo-like kinase1 (PLK1) was identified as the kinase whose downregulation interfered with cell proliferation. Both PLK1 siRNA and two specific PLK1 inhibitors (onvansertib and volasertib) were able to inhibit cell growth, induce apoptosis and block cells in the G2/M phase of the cell cycle. We evaluated, in vitro, the combinations of PLK1 inhibitors and different chemotherapeutic drugs currently used in the treatment of mEOC, and we observed a synergistic effect of PLK1 inhibitors and antimitotic drugs. When translated into an in vivo xenograft model, the combination of onvansertib and paclitaxel resulted in stronger tumor regressions and in a longer mice survival than the single treatments. These effects were associated with a higher induction of mitotic block and induction of apoptosis, similarly to what was observed in vitro. These data suggest that the combination onvansertib/paclitaxel could represent a new active therapeutic option in mEOC. [ABSTRACT FROM AUTHOR]

Mucinous ovarian cancer (MOC) is a rare subtype of epithelial ovarian carcinoma (EOC). Whereas all EOC subtypes are addressed in the same way, MOC is a distinct entity. Appreciating the pathological features and genomic profile of MOC may result in the improvement in management and, hence, the prognosis. Distinguishing primary MOC from metastatic mucinous carcinoma can be challenging but is essential. Early-stage MOC carries an excellent prognosis, with advanced disease having a poor outcome. Surgical management plays an essential role in the early stage and in metastatic disease. Chemotherapy is usually administered for stage II MOC and beyond. The standard gynecology protocol is frequently used, but gastrointestinal regimens have also been administered. As MOC is associated with multiple molecular alterations, targeted therapy could be the answer to treat this disease. [ABSTRACT FROM AUTHOR]