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PURPOSE OF REVIEW: Mucinous ovarian cancers (MOCs) are categorized into infiltrative and expansile subtypes. These subtypes have different characteristics and prognoses. Patients with clinical early-stage disease of both subtypes currently undergo surgical staging (peritoneal washing, biopsies, omentectomy). Peritoneal and lymph node metastases of expansile MOC are rare, but whereas lymph node sampling (LNS) is omitted in these patients, peritoneal staging is not. Therefore, we collected all available MOC data to determine whether staging surgeries could safely be omitted in clinical early-stage expansile and infiltrative MOC. RECENT FINDINGS: Current literature confirms that peritoneal metastases are rare in expansile MOC: more than 90% had early-stage disease. Only 3.4% of the patients with clinical early-stage expansile MOC had positive peritoneal washings at surgical staging. Patients with infiltrative MOC were diagnosed more frequently with advanced-stage disease (21-54%). Moreover, upstaging clinical early-stage infiltrative MOC based on positive cytology, peritoneum and omentum metastases occurred in 10.3% of the patients. Therefore, we recommend that patients with early-stage infiltrative MOC undergo peritoneal staging and LNS. However, in addition to omitting LNS, we can also safely recommend omitting peritoneal staging in patients with early-stage expansile MOC. SUMMARY: Peritoneal metastases are rare in clinical early-stage expansile MOC and peritoneal staging can therefore safely be omitted.

Objective: Epithelial ovarian cancer (EOC) is the second most common malignancy among women. Mucinous ovarian carcinoma ( mOC) is the rare subtype comprising only 3–5% of all EOC. This study examines the expression of BMI-1 as a potential target for therapeutic approaches in advanced stages of mOC. Methods: The selection of eighteen cases of mucinous ovarian cancer was based on the availability of paraffin-embedded tissue and the clinicopathology. We analysed gene set and transcription factor enrichment. Immunohistochemistry was performed for anti–Bmi-1 antibody. We compared the expression levels of high and low BMI-1 expression groups with the patient's age, FIGO stage, lymph node status, family history, and survival. A cell viability assay and western blot analysis were investigated to demonstrate the clinical relevance of the findings using high-grade serous (HGSC) and mOC cell lines. Results: There was no significant link between BMI1 expression and patient age, FIGO stage, lymph node state, or family history. Likewise, there was no significant association with progression-free survival (p=0.418). As a result of carboplatin treatment, HGSC TYK-nu, OVHASO, and mOC lines COV644 and EFO-27 showed significant reductions in cell viability. A Western blot analysis revealed different levels of expression among all cell lines. Conclusion: BMI-1 might be a promising therapeutic target in some ovarian cancer patients, including mOC patients., Zielsetzung: Das epitheliale Ovarialkarzinom (EOC) ist die zweithäufigste Malignität bei Frauen. Das muzinöse Ovarialkarzinom (mOC) ist ein seltener Subtyp, der lediglich 3-5 % aller EOC ausmacht. In dieser Studie wurde die Expression von BMI-1 als potenzielles Ziel therapeutischer Ansätze bei fortgeschrittenen Stadien des mOC untersucht. Methoden: Die Auswahl von achtzehn Fällen von muzinösem Ovarialkarzinom beruhte auf der Verfügbarkeit von in Parfaffin eingebettetem Gewebe und der klinikopathologie. Wir analysierten die Anreicherung des Gensets und des Transkriptionsfaktors. Für den anti-BMI-1-Antikörper wurde eine Immunohistochemie durchgeführt. Wir verglichen die Expressionsniveaus von Expressionsgruppen mit hohem und niedrigem BMI-1-Niveau mit dem Alter, FIGO- Stadium, Stadium der Lymphknoten, der Familienanamnese und der Überlebensrate der Patientinnen. Ein Zelllebensfähigkeitstest und eine Western-Blot-Analyse wurden durchgeführt, um die klinische Relevanz der Befunde unter Verwendung seröser high-grade Zelllinien (HGSC) und mOC Zelllinien zu zeigen. Ergebnisse: Zwischen der BMI-1-Expression und dem Alter, dem FIGO-Stadium, dem Stadium der Lymphknoten oder der Familienanamnese der Patientinnen bestand keine signifikante Korrelation. Ebenso gab es keinen signifikanten Zusammenhang mit progressionsfreiem Überleben (p=0,418). Die Behandlung mit Carboplatin führte bei HGSC TYK-nu, OVHASO sowie den mOC Zelllinien COV644 und EFO-27 zu signifikanten Verringerungen der Zellviabilität. Eine Western-Blot- Analyse zeigte bei allen Zelllinien verschiedene Expressionsniveaus. Schlussfolgerung: BMI-1 könnte bei der Behandlung einiger Patientinnen mit Ovarialkarzinom einschließlich mOC Patientinnen ein vielversprechender therapeutischer Angriffspunkt sein.

Objective Considering the clinical evidence of BRAF inhibitors that can treat melanoma patients successfully, we aimed to investigate the status of BRAF mutations of primary mucinous ovarian carcinomas (MOC) in Taiwanese women, and apply the emerging paradigm classification of BRAF mutation groups. Materials and methods 20 archived primary MOC samples were analyzed. The BRAF mutations of activation segment (exon 15), CR3 (conserved regions 3), kinase domain of the BRAF gene were analyzed using the highly sensitive BRAF mutant enriched kit (FemtoPath®) with Sanger sequencing method. Additionally, we extended our prior reported data of HER2 aberrations and KRAS mutation into this study in order to compare with the status of BRAF mutation. Results Of them (n = 20), 16 (80%) harbored BRAF missense mutations. Their mutation profile and case number (n) were categorized as (1) class I: V600E (n=1), V600M (n = 1); (2) class II: A598V (n = 1), T599I (n = 10); (3) class III: none (n = 0); and (4) unclassified variants: S602F (n = 2), T599I/S602F (n = 1). The BRAF S602F is novel. The prevalence of BRAF mutation is significantly higher than either HER2 mutation (80% vs. 35%; p = 0.022) or HER2 amplification (80% vs. 35%; p = 0.022). However, the mutation rates of BRAF and KRAS were not significantly different (80% vs. 60%; p = 0.289). Conclusion Activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive. However, they may even have a synergistic effect in tumorigenesis. BRAF mutation is not uncommon in primary MOC of Taiwanese. The BRAF mutant (T599I) stands the majority. We suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage primary MOC patients carrying different classes of BRAF mutation.

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.

Primary mucinous ovarian carcinomas (MOC) are notoriously difficult to distinguish from mucinous carcinomas metastatic to the ovary (mMC). Studies performed on small cohorts reported algorithms based on tumor size and laterality to aid in distinguishing MOC from mMC. We evaluated and improved these by performing a large-scale, nationwide search in the Dutch Pathology Registry. All registered pathology reports fulfilling our search criteria concerning MOC in the Netherlands from 2000 to 2011 were collected. Age, histology, laterality, and size were extracted. An existing database covering the same timeline containing tumors metastatic to the ovary was used, extracting all mMC, age, size, laterality, and primary tumor location. Existing algorithms were applied to our cohort. Subsequently, an algorithm based on tumor histology, laterality, and a nomogram based on age and size was created for differentiating MOC and mMC. We identified 735 MOC and 1018 mMC. Patients with MOC were significantly younger and MOC were significantly larger and more often unilateral than mMC. Signet ring cell carcinomas were rarely primary. Our algorithm used signet ring cell histology, bilaterality, and a nomogram integrating patient age and tumor size to diagnose mMC. Sensitivity and specificity for mMC was 90.1% and 59.0%, respectively. Applying existing algorithms on our cohort yielded a far lower sensitivity. The algorithm described here using tumor histology, laterality, size, and patient age has higher sensitivity but lower specificity compared to earlier algorithms and aids in indicating tumor origin, but for conclusive diagnosis, careful integration of morphology, immunohistochemistry, and clinical and imaging data is recommended. Electronic supplementary material The online version of this article (10.1007/s00428-018-2504-0) contains supplementary material, which is available to authorized users.

Contains fulltext : 155223.pdf (Publisher’s version ) (Open Access) A significant proportion of ovarian malignancies consists of metastatic tumors, with a wide variety in site of origin. Differentiating between a primary and metastatic malignancy of the ovaries can be difficult and misdiagnosis might have considerable impact on both treatment and prognosis. To further examine the origin of malignancies metastatic to the ovary, we performed a large-scale, nationwide search for ovarian metastases in the Dutch Pathology Registry (PALGA). All pathology reports concerning malignancies metastatic to the ovary and associated primary tumors in the Netherlands between 2000 and 2010 were collected. Age, year of diagnosis, tumor type, location of the primary tumor, and side of the ovarian tumor were extracted from the database. We identified 2312 patients fulfilling our selection criteria. The most common primary malignancy sites were colon (33.2%), endometrium (17.1%), breast (14.3%), appendix (7.3%), and stomach (4.5%). The metastases were most frequently bilateral (46.3%) followed by unilateral metastases in the right (26.7%) and left ovary (19.8%), while side was unknown in 7.2% of cases. Of colorectal carcinomas, only 40.2% metastasized bilaterally, compared to 63.9% of breast, 62.9% of gastric, and 58.9% of appendix carcinomas. Left-sided colorectal carcinomas most often metastasized to the left ovary (p < 0.0001). We found colon carcinomas to be most frequently responsible for metastases to the ovaries, followed by endometrial and breast carcinomas. Metastases from breast, stomach, and appendix carcinomas were mostly bilateral, whereas metastases from colorectal carcinomas were mostly unilateral. The mechanisms underlying preferred sites for metastasis or side remain unclear.

Objective The main aim of this study was to evaluate cancer antigen 125 (CA125)/carcinoembryonic antigen (CEA) ratio (CCR), as a reliable marker to differentiate ovarian mucinous carcinoma from other epithelial ovarian carcinomas (EOCs), namely serous, clear cell, and endometrioid carcinomas. Methods Female patients suffering from different kinds of EOCs whom were subjected to elective surgery at the Gangnam Severance Hospital between January 2008 and December 2016, were included in this study. The serum levels of CA125 and CEA were assayed using commercially available kits per the manufacturer''s instructions. Results The CCR in mucinous carcinoma (mean 32.1) was significantly lower than that of clear cell (mean 235.0) and endometrioid carcinoma (mean 427.0) in stage I (all P

Objective Mucinous ovarian carcinoma (MOC) is an uncommon subtype of epithelial ovarian cancers, and the pathogenesis is still poorly understood because of its rarity. We conducted a gene set-based analysis to investigate the pathogenesis of MOC by integrating microarray gene expression datasets based on the regularity of functions defined by gene ontology or canonical pathway databases. Materials and methods Forty-five pairs of MOC and normal ovarian tissue sample gene expression profiles were downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database. The gene expression profiles were converted to the gene set regularity indexes by measuring the change of gene expression ordering in a gene set. Then the pathogenesis of MOC was investigated with the differences of function regularity with the gene set regularity indexes between the MOC and normal control samples. Results The informativeness of the gene set regularity indexes was sufficient for machine learning to accurately recognize and classify the functional regulation patterns with an accuracy of 99.44%. The statistical analysis revealed that the GTPase regulators and receptor tyrosine kinase erbB-2 (ERBB2) were the most important aberrations; the exploratory factor analysis revealed phosphoinositide 3-kinase-activating kinase, G-protein coupled receptor pathway, oxidoreductase activity, immune response, peptidase activity, regulation of translation, and transport and channel activity were also involved in the pathogenesis of MOC. Conclusion Investigating the pathogenesis of MOC with the functionome provided a comprehensive view of the deregulated functions of this disease. In addition to GTPase regulators and ERBB2, a plenty of deregulated functions such as phosphoinositide 3-kinase, G-protein coupled receptor pathway, and immune response also participated in the interaction network of MOC pathogenesis.