MONITOR VII: Treatment strategies of low grade ovarian carcinomas – A German survey of the Charité – Berlin and Kliniken Essen Mitte with support of the study groups NOGGO and AGO

The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.

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Heterogeneity in PD-L1 expression and CD8+ infiltrates in low grade versus high grade serous ovarian carcinomas

10.26226/morressier.578f37fdd462b8028d88f8a5 ◽

2016 ◽

Cited By ~ 1

Author(s):

Oriane Descamps-Dudez

Keyword(s):

Low Grade ◽

High Grade ◽

Ovarian Carcinomas ◽

Grade Versus

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MOLECULAR AND GENETIC SUBTYPES OF OVARIAN CANCER: PROSPECTS FOR FURTHER STUDIES

Problems in oncology ◽

10.37469/0507-3758-2019-65-1-56-62 ◽

2019 ◽

Vol 65 (1) ◽

pp. 56-62

Author(s):

Alisa Villert ◽

Larisa Kolomiets ◽

Natalya Yunusova ◽

Yevgeniya Fesik

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

Molecular Subtypes ◽

Survival Rates ◽

Consensus Algorithm ◽

Histopathological Diagnosis ◽

Low Grade ◽

High Grade ◽

Ovarian Carcinomas ◽

Genetic Subtypes

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.

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Immunohistochemical Biomarkers as a Surrogate of Molecular Analysis in Ovarian Carcinomas: A Review of the Literature

Diagnostics ◽

10.3390/diagnostics11020199 ◽

2021 ◽

Vol 11 (2) ◽

pp. 199 ◽

Cited By ~ 1

Author(s):

Giacomo Santandrea ◽

Simonetta Piana ◽

Riccardo Valli ◽

Magda Zanelli ◽

Elisa Gasparini ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Molecular Analysis ◽

Immunohistochemical Analysis ◽

Cost Effective ◽

Mucinous Carcinoma ◽

Serous Carcinoma ◽

Malignant Neoplasms ◽

Low Grade ◽

Ovarian Carcinomas ◽

Novel Target

The term “ovarian carcinoma” encompasses at least five different malignant neoplasms: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, mucinous carcinoma, and clear cell carcinoma. These five histotypes demonstrated distinctive histological, molecular, and clinical features. The rise of novel target therapies and of a tailored oncological approach has demanded an integrated multidisciplinary approach in the setting of ovarian carcinoma. The need to implement a molecular-based classification in the worldwide diagnostic and therapeutic setting of ovarian cancer demanded a search for easy-to-use and cost-effective molecular-surrogate biomarkers, relying particularly on immunohistochemical analysis. The present review focuses on the role of immunohistochemistry as a surrogate of molecular analysis in the everyday diagnostic approach to ovarian carcinomas.

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Clinical Utility of Real-Time Targeted Molecular Profiling in the Clinical Management of Ovarian Cancer: The ALLOCATE Study

JCO Precision Oncology ◽

10.1200/po.19.00019 ◽

2019 ◽

pp. 1-18

Author(s):

Olga Kondrashova ◽

Gwo-Yaw Ho ◽

George Au-Yeung ◽

Leakhena Leas ◽

Tiffany Boughtwood ◽

...

Keyword(s):

Ovarian Cancer ◽

Real Time ◽

Targeted Therapies ◽

Clinical Management ◽

Clinical Utility ◽

Advanced Ovarian Cancer ◽

Molecular Profiling ◽

Molecular Testing ◽

Low Grade ◽

Ovarian Carcinomas

PURPOSE The ALLOCATE study was designed as a pilot to demonstrate the feasibility and clinical utility of real-time targeted molecular profiling of patients with recurrent or advanced ovarian cancer for identification of potential targeted therapies. PATIENTS AND METHODS A total of 113 patients with ovarian cancer of varying histologies were recruited from two tertiary hospitals, with 99 patient cases suitable for prospective analysis. Targeted molecular and methylation profiling of fresh biopsy and archived tumor samples were performed by screening for mutations or copy-number variations in 44 genes and for promoter methylation of BRCA1 and RAD51C. RESULTS Somatic genomic or methylation events were identified in 85% of all patient cases, with potentially actionable events with defined targeted therapies (including four resistance events) detected in 60% of all patient cases. On the basis of these findings, six patients received molecularly guided therapy, three patients had unsuspected germline cancer–associated BRCA1/ 2 mutations and were referred for genetic counseling, and two intermediate differentiated (grade 2) serous ovarian carcinomas were reclassified as low grade, leading to changes in clinical management. Additionally, secondary reversion mutations in BRCA1/ 2 were identified in fresh biopsy samples of two patients, consistent with clinical platinum/poly (ADP-ribose) polymerase inhibitor resistance. Timely reporting of results if molecular testing is done at disease recurrence, as well as early referral for patients with platinum-resistant cancers, were identified as factors that could improve the clinical utility of molecular profiling. CONCLUSION ALLOCATE molecular profiling identified known genomic and methylation alterations of the different ovarian cancer subtypes and was deemed feasible and useful in routine clinical practice. Better patient selection and access to a wider range of targeted therapies or clinical trials will further enhance the clinical utility of molecular profiling.

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The chemotherapy and radiation in low-grade myofibroblastic sarcoma: is there a role?

10.21203/rs.2.23274/v1 ◽

2020 ◽

Author(s):

Yao Xu ◽

Guijun Xu ◽

Xin Wang ◽

Min Mao ◽

Haixiao Wu ◽

...

Keyword(s):

Prognostic Factors ◽

Surgical Treatment ◽

Head And Neck ◽

Radiation Treatment ◽

Treatment Strategies ◽

Neck Region ◽

Low Grade ◽

Myofibroblastic Sarcoma ◽

Kaplan Meier ◽

Cox Proportional Hazard Regression

Abstract Background: Low-grade myofibroblastic sarcoma (LGMS) is a rare entity with a predilection in the head and neck. There are still no optimal treatment strategies for LGMS. We aimed to investigate the role of chemotherapy and radiation treatment for LGMS. Survival estimate was performed and prognostic factors were identified.Methods: Based on the Surveillance, Epidemiology, and End Result (SEER) database, LGMS patients diagnosed between 2001 and 2015 were involved in our study. Kaplan-Meier curves and log-rank tests were used to estimate overall survival. Cox proportional hazard regression model was performed to identify prognostic factors.Results: A total of 96 eligible patients with LGMS were included, among which 86 (89.6%) received surgical treatment. Twenty-eight (29.2%) patients received radiation treatment while chemotherapy was offered to 20 (10.4%) patients. The median age was 55.0 years old with 22 cases occurred in head and neck region. The mean OS was 125.2 (95%CI 106.3-144.2) months while 1-, 3-, 5- and 10-year OS rates were 88%, 77%, 70% and 59%, respectively. Age older than 60 years, positive nodal status and no surgical treatment were independent prognostic factors for patients with LGMS. Chemotherapy and radiation were not independent prognostic factors for LGMS.Conclusions: Several prognostic factors for LGMS were revealed in this study. Surgical resection is the main therapy while chemotherapy and radiation showed limited effects on survival improvement. Thus, chemotherapy and/or radiation should not be routinely performed in LGMS.

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Nasopharyngeal Hyalinizing Clear Cell Carcinoma: A Case Report and Review of the Literature

Allergy & Rhinology ◽

10.1177/2152656719889030 ◽

2019 ◽

Vol 10 ◽

pp. 215265671988903 ◽

Cited By ~ 1

Author(s):

Madison J. Malfitano ◽

Meghan N. Norris ◽

Wesley H. Stepp ◽

Griffin D. Santarelli ◽

T. Danielle Samulski ◽

...

Keyword(s):

Case Report ◽

Salivary Glands ◽

Clear Cell ◽

Malignant Tumors ◽

Treatment Strategies ◽

Low Grade ◽

Minor Salivary Glands ◽

Presenting Symptoms ◽

Nasopharyngeal Mass ◽

The Right

Background Hyalinizing clear cell carcinomas (HCCCs) are rare, low-grade, malignant tumors which most often arise from the minor salivary glands primarily in palate and tongue but can arise in any location with minor salivary glands including the nasopharynx. Methods A case report of primary nasopharyngeal HCCC is presented. Because of the rarity of this tumor and location, a literature search was conducted to determine the most common presenting symptoms, treatment strategies, and outcomes. Results A 48-year-old man underwent biopsy of a 4.5 cm mass of the right nasopharynx with pathology suggesting an intermediate grade mucoepidermoid carcinoma. After discussing management with the patient, an endoscopic resection was performed. Final pathology revealed an HCCC which was confirmed after negative Mastermind-like 2 (MAML2) and positive Ewing sarcoma breakpoint region 1 (ESWR1) gene rearrangements on fluorescence in situ hybridization (FISH) studies. Literature review of other nasopharyngeal HCCC cases shows diverse presentation and overall excellent prognosis through surgical and radiation therapy. Conclusion HCCCs are rare, low-grade malignant tumors of the minor salivary glands and can present as a nasopharyngeal mass. Presenting symptoms are diverse but frequently involve otologic and sinonasal disturbances. HCCC is an indolent tumor with an excellent prognostic outcome when treated appropriately with surgical resection and adjuvant radiotherapy.

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P53 and bcl-2 assessment in serous ovarian carcinoma

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2007.01000.x ◽

2008 ◽

Vol 18 (2) ◽

pp. 241-248 ◽

Cited By ~ 8

Author(s):

J. E. Palmer ◽

L. J. Sant Cassia ◽

C. J. Irwin ◽

A. G. Morris ◽

T. P. Rollason

Keyword(s):

Prognostic Value ◽

Disease Free Survival ◽

Ovarian Tumors ◽

Early Event ◽

Low Grade ◽

Ovarian Carcinomas ◽

Study Objective ◽

P53 Expression ◽

Response To Chemotherapy ◽

Clinicopathologic Parameters

The study objective was to determine the prognostic value of assessment of staining of p53 and bcl-2 in a well-selected group of serous ovarian carcinomas. Immunohistochemical detection was used to identify both p53 and bcl-2 positive tumors. One hundred thirty-two tumors were analyzed for positivity of staining, grade of staining intensity, and for p53 alone, percent expression rates. These were analyzed alongside traditional clinicopathologic parameters for their ability to predict overall survival (OS), disease-free survival (DFS), and response to chemotherapy (CR). Univariate COX analysis revealed percent p53 expression (P= 0.012) and p53 grade (P= 0.01) to be significant predictors of DFS. Neither the p53 nor bcl-2 measurement parameters were found significant for OS or prediction of CR. On multivariate analysis, incorporating clinicopathologic parameters, p53 parameters did not retain independent significance for any outcome measure. As in primary reported studies, bcl-2 was not found to be of clear independent prognostic value in this group of ovarian tumors. If mutation of p53 and its consequent overexpression is an early event in ovarian tumorigenesis, then p53 assessment may prove useful prognostically in the assessment of either low-grade ovarian carcinomas, as a possible indicator for progression, or in early-stage ovarian tumors, as a marker of tumor aggression or likelihood of recurrence. p53 analysis of a larger group of stage I ovarian tumors would be desirable to further explain the potential association with DFS.

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Cellular Alteration of the Oral Mucosa due to Orthodontic Appliances and Tobacco Smoking: A Cytomorphometric Study

Journal of College of Medical Sciences-Nepal ◽

10.3126/jcmsn.v15i3.22620 ◽

2019 ◽

Vol 15 (3) ◽

pp. 206-210

Author(s):

Vinay Marla ◽

Dharanidhar Baral ◽

Prabhat Ranjan Pokharel ◽

Ashish Shrestha ◽

Rajesh Gyawali ◽

...

Keyword(s):

Oral Mucosa ◽

Tobacco Smoking ◽

Orthodontic Treatment ◽

Study Groups ◽

Cell Diameter ◽

Orthodontic Appliances ◽

Low Grade ◽

Nuclear Area ◽

Mucosal Cells ◽

Orthodontic Patients

Introduction: Fixed orthodontic treatment causes chronic low grade irritation on the oral mucosa. Tobacco smoking is considered to be a risk factor in the development of oral cancer. This study involves a cytomorphometric analysis on the buccal mucosal cells in patients undergoing fixed orthodontic treatment who are tobacco smokers. Methods: Exfoliated buccal mucosal cells were obtained from orthodontic patients (smokers & non-smokers) as well as smokers and non-smokers who are not undergoing any orthodontic treatment. Smears were stained with rapid PAP stain and digital images of 50 cells were analysed using the Image J software. Results: Statistical analysis revealed that there were significant increase in the values of nuclear and cell diameter between non-smokers undergoing orthodontic treatment and smokers (p<0.001 & p=0.014 respectively), and between non-smokers undergoing orthodontic treatment and smokers undergoing orthodontic treatment (p<0.001 & p=0.015 respectively). Also, nuclear area and cell area showed significant differences between many of the study groups. Conclusion: It can be concluded that there are nuclear and cellular alterations in patients undergoing fixed orthodontic treatment who are smokers

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Ultrasound, macroscopic and histological features of serous epithelial ovarian carcinomas

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-001473 ◽

2020 ◽

pp. ijgc-2020-001473

Author(s):

Paola Romeo ◽

Damiano Arciuolo ◽

Maria Cristina Moruzzi ◽

Francesca Moro

Keyword(s):

Ovarian Carcinoma ◽

Low Grade ◽

High Grade ◽

Ovarian Carcinomas ◽

Histological Features ◽

Serous Ovarian Carcinoma ◽

Epithelial Ovarian Carcinomas

We present a video showing two cases of serous epithelial ovarian carcinomas. The first video shows clinical, ultrasound, macroscopic, and histological features of a patient with high grade serous ovarian carcinoma. The second video presents clinical, ultrasound, macroscopic, and histological features of a patient with low grade serous ovarian carcinoma.

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