Molecular profiling of atypical endometriosis as premalignant lesions of ovarian cancer

2020 ◽  
Vol 159 ◽  
pp. 345
Author(s):  
D. Chung ◽  
D.B. Chay ◽  
H. Shin ◽  
W. Yang ◽  
H. Cho ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Profiling ◽  
Premalignant Lesions ◽  
Atypical Endometriosis

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

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.

scholarly journals Predictive factors of endometriosis progression into ovarian cancer

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Ján Varga ◽  
Alžbeta Reviczká ◽  
Hedviga Háková ◽  
Peter Švajdler ◽  
Miroslava Rabajdová ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Predictive Factors ◽  
Control Group ◽  
Histopathological Analysis ◽  
Genes Expression ◽  
Patients At Risk ◽  
Conventional Cytogenetics ◽  
Normal Cytogenetics ◽  
Atypical Endometriosis

Abstract Background In recent years, the endometriosis has overcome a noteworthy renaissance in the recognition of its potential. In certain patients, a demonstrable malignant progression of ectopic foci leading to development of ovarian cancer is seen. The knowledge of endometriosis overthrow background into endometriosis associated ovarian cancer is of paramount importance for selection of patients at risk. The goal of the presented study was to review a malignant potential of the endometriosis and to specify predictive factors of endometriosis progression into ovarian cancer. Altogether 189 patients were included in the study. Conventional cytogenetics as well as measurement of transcriptional activity of CTNNB1 (β-catenin) and HIF1A (HIF1-α) genes were prospectively studied in 60 endometriosis patients and 50 control group patients. The retrospective histopathological analysis was performed in 19 endometriosis associated ovarian cancer patients and 60 patients with histologically confirmed endometriosis. Results Five endometriosis patients showed a deviation from normal cytogenetics finding without affecting of their phenotype. In 6 cases of endometriosis associated ovarian cancer ectopic endometrium was not confirmed. The remaining 13 cases demonstrated either benign or atypical endometriosis or even structures of borderline carcinoma. Atypical endometriosis was histologically confirmed in 20% of 60 endometriosis patients. Determination of gene expression (CTNNB1, HIF1A) formed two subgroups. Transcriptionally incipient endometriosis subgroup with insignificant genes expression compared to control group. In transcriptionally evident endometriosis subgroup were genes expressions significantly higher compared to control group (p < 0.01) as well as transcriptionally incipient endometriosis subgroup (p < 0.05). Conclusions Significant structural abnormalities of chromosomes are not included in genetic rigging of endometriosis patients. Atypical endometriosis represents a histopathologically detectable intermediate of endometriosis progression. Determination of genes expression CTNNB1 and HIF1A helps to allocate risk patients with endometriosis where more precise management is needed.

scholarly journals Evaluation of PTEN and Ki67 Expression in Typical and Atypical Endometriosis and Endometriosis Associated Ovarian Cancer

2020 ◽  
Vol 21 (11) ◽  
Author(s):  
Mojgan Akbarzadeh-Jahromi ◽  
Zahra Zare ◽  
Fatemeh Sari Aslani ◽  
Simin Torabinezhad
Keyword(s):  
Ovarian Cancer ◽  
Precancerous Lesion ◽  
Early Event ◽  
P Value ◽  
Ovarian Endometriosis ◽  
Ki 67 ◽  
Pten Loss ◽  
Epithelial Component ◽  
Increased Risk ◽  
Atypical Endometriosis

Background: Several studies reported that endometriosis is associated with an increased risk of ovarian cancer. Atypical endometriosis is common in patients with endometriosis-associated ovarian, which might be considered as a precancerous lesion. Objectives: This study aimed to assess ki67 and PTEN expression in endometriosis associated ovarian cancer (EAOC), atypical endometriosis, and typical endometriosis. Methods: In this study, all H & E slides of 260 ovarian endometriosis cases were reviewed. And 25 cases were diagnosed with atypical endometriosis. Forty-one typical endometrioses and 24 ovarian cancers with endometriosis were included. We assessed PTEN and Ki67 immunoexpression in epithelial and stromal cells. Results: The prevalence of atypical endometriosis was about 9%. PTEN loss was found in 12 (out of 24 or 50%) of EAOC, 2 (out of 25; 8%) of atypical endometriosis, and none of the typical endometriosis. In all 12 PTEN loss cases, the PTEN loss pattern in endometriosis adjacent to ovarian cancer was similar to that of ovarian cancer. A total of 7.3% of typical endometriosis and 8% atypical endometriosis and 33.3% of EAOC had Ki67 staining in more than 50% of the epithelial component. Both typical and atypical endometriosis showed similar PTEN loss and Ki 67 staining (in more than 50% of the epithelial component) (P value > 0.05), and both of them were different from EAOC (P value < 0.05). Conclusions: The PTEN loss pattern in endometriosis adjacent to ovarian cancer was similar to that of ovarian cancer. The result indicated that PTEN loss could be an early event in the tumor development pathway from endometriosis to ovarian cancer.

Molecular Profiling and Commercial Predication Assays in Ovarian Cancer: Still Not Ready for Prime Time?

2014 ◽  
pp. 139-147 ◽  
Author(s):  
Elise C. Kohn
Keyword(s):  
Ovarian Cancer ◽  
Germ Line ◽  
Molecular Profiling ◽  
Added Value ◽  
Prime Time ◽  
Cancer Type ◽  
Brca1 And Brca2 ◽  
Major Barrier ◽  
The Individual

Short of early detection to allow curative primary intervention, the other major barrier to further success in treatment of ovarian cancers is matching the best treatment to the proper ovarian cancer type and to the individual patient. There are several decades of experience applying in vitro chemoresponse testing for solid tumors including ovarian cancer. This concept, first described in 1979, has yet to receive level one evidence supporting its application, despite the testing of numerous assays commercially as well as in academic centers and its use for tens of thousands of patients at a significant cost. The approach—rather than undergoing rigorous scientific examination—is now being muddied by the development of commercial molecular profiling assays from which treatment suggestions are provided. Molecular profiling as a research tool has added value to our understanding and treatment of patients with ovarian cancer. Morphologic and histochemical characterizations coupled now with increasing knowledge of ovarian cancer type-specific molecular patterns is improving our ability to properly diagnosis ovarian cancer type and thus guide therapy. With the exception of the role of germ-line and possibly somatic BRCA1 and BRCA2 mutations and their true predictiveness for probable response to poly(ADP-ribose) polymerase inhibition, molecular typing and profiling has yet to identify druggable molecular targets in ovarian cancer. Its use should be continued as a research and learning tool, and its results should be subjected to clinical trial validation. For very different reasons, neither chemoresponse assays nor molecular profiling are ready for prime time, yet.

scholarly journals Integrated Molecular Profiling Studies to Characterize the Cellular Origins of High-Grade Serous Ovarian Cancer

2018 ◽  
Author(s):  
Kate Lawrenson ◽  
Marcos A.S. Fonseca ◽  
Felipe Segato ◽  
Janet M. Lee ◽  
Rosario I. Corona ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Cells ◽  
Tumor Development ◽  
Molecular Profiling ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cell Of Origin ◽  
Ovarian Cancers ◽  
Integrative Analyses ◽  
Ovarian Surface Epithelial

AbstractHistorically, high-grade serous ovarian cancers (HGSOCs) were thought to arise from ovarian surface epithelial cells (OSECs) but recent data implicate fallopian tube secretory epithelial cells (FTSECs) as the major precursor. We performed transcriptomic and epigenomic profiling to characterize molecular similarities between OSECs, FTSECs and HGSOCs. Transcriptomic signatures of FTSECs were preserved in most HGSOCs reinforcing FTSECs as the predominant cell-of-origin; though an OSEC-like signature was associated with increased chemosensitivity (Padj= 0.03) and was enriched in proliferative-type tumors, suggesting a dualistic model for HGSOC origins. More super-enhancers (SEs) were shared between FTSECs and HGSOCs than between OSECS and HGSOCs (P< 2.2 × 10−16). SOX18, ELF3 and EHF transcription factors (TFs) coincided with HGSOC SEs and represent putative novel drivers of tumor development. Our integrative analyses support a predominantly fallopian origin for HGSOCs and indicate tumorigenesis may be driven by different TFs according to cell-of-origin.

scholarly journals Next Generation Sequencing of Tumor and Matched Plasma Samples: Identification of Somatic Variants in ctDNA From Ovarian Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Ana Barbosa ◽  
Pedro Pinto ◽  
Ana Peixoto ◽  
Joana Guerra ◽  
Manuela Pinheiro ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Next Generation Sequencing ◽  
Molecular Profiling ◽  
Post Treatment ◽  
Plasma Samples ◽  
Next Generation ◽  
Somatic Variant ◽  
Treatment Naïve ◽  
Ctdna Analysis ◽  
Generation Sequencing

Genetic testing to detect somatic alterations is usually performed on formalin-fixed paraffin-embedded tumor samples. However, tumor molecular profiling through ctDNA analysis may be particularly interesting with the emergence of targeted therapies for ovarian cancer (OC), mainly when tumor is not available and biopsy is not viable, also allowing representation of multiple neoplastic subclones. Using a custom panel of 27 genes, next-generation sequencing (NGS) was performed on tumor and matched plasma samples from 96 OC patients, which were combined in two groups (treatment naive and post-treatment). Overall, at least one somatic variant present in the tumor sample was also detected in the matched plasma sample in 35.6% of the patients, a percentage that increased to 69.6% of the treatment naive patients and 83.3% of those with stage IV disease, showing the potential of ctDNA analysis as an alternative to identify somatic variants in these patients, namely those that have predictive value for targeted therapy. In fact, of the two treatment-naive patients with somatic BRCA1 variants identified in tumor samples, in one of them we detected in ctDNA a BRCA1 somatic variant that was present in the tumor with a VAF of 53%, but not in the one that had a VAF of 5.4%. We also showed that ctDNA analysis has a complementary role to molecular unraveling of inter- and intra-tumor heterogeneity, as exemplified by one patient diagnosed with bilateral OC in which different somatic variants from both tumors were detected in ctDNA. Interestingly, as these bilateral tumors shared a rare combination of two of the three variants identified in ctDNA, we could conclude that these morphologically different tumors were clonally related and not synchronous independent neoplasias. Moreover, in the post-treatment group of patients with plasma samples collected after surgery, those with detectable somatic variants had poor prognosis when compared with patients with no detectable somatic variants, highlighting the potential of ctDNA analysis to identify patients at higher risk of recurrence. Concluding, this study demonstrated that somatic variants can be detected in plasma samples of a significant proportion of OC patients, supporting the use of NGS-based ctDNA testing for noninvasive tumor molecular profiling and to stratify patients according to prognosis.

scholarly journals Long-Term Follow-Up after Surgical Management for Atypical Endometriosis: A Series of Nine Cases

2019 ◽  
Vol 12 (1) ◽  
pp. 76-83 ◽  
Author(s):  
Yasuhito Tanase ◽  
Ryuji Kawaguchi ◽  
Tomoko Uchiyama ◽  
Hiroshi Kobayashi
Keyword(s):  
Ovarian Cancer ◽  
Clinical Characteristics ◽  
Median Overall Survival ◽  
Case Series ◽  
Endometrioid Carcinoma ◽  
Long Term Follow Up ◽  
Laparoscopic Cystectomy ◽  
Atypical Endometriosis

Background and Objective: Atypical endometriosis is reported to possess a precancerous potential attributed to premalignant changes characterized by cytological atypia and architecture proliferation. Although the coexistence of atypical endometriosis and neoplasms has been reported, cases of atypical endometriosis transformation to carcinoma are rarely reported. The purpose of this case series was to evaluate the prognosis of atypical endometriosis. Subjects and Methods: Data from nine women who underwent surgical treatment including cystectomy and salpingo-oophorectomy with or without hysterectomy and diagnosed with atypical endometriosis was analyzed. Between January 2006 and January 2018, the clinical characteristics and prognosis of atypical endometriosis were evaluated. Results: During the follow-up period, eight of nine patients with atypical endometriosis did not develop malignant epithelial tumors, although one patient developed endometrioid carcinoma, grade 1, 48 months after her right laparoscopic cystectomy. The median overall survival period for all patients was 68 (range 13–131) months. Conclusion: When we encounter the cases of atypical endometriosis, it is necessary to consider the possibility of ovarian cancer and carefully follow those cases for long periods.

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