Publications by authors named "Marie-Aude Le-Frere-Belda"

Article Synopsis
  • The classification of uterine sarcomas is evolving with the discovery of new types linked to specific genetic changes, categorizing them into complex genomic and simple genomic sarcomas.
  • The most common types include leiomyosarcomas and endometrial stromal sarcomas, with various histological subtypes that have differing degrees of aggression.
  • Recent advances in molecular diagnostics and targeted therapies are enhancing the identification and treatment strategies for these tumors.
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Recommendations for clinical practice Nice/Saint-Paul-de-Vence 2022-2023 : Management of advanced/relapsing endometrial cancer Since the first recommendations in 2020 concerning metastatic and/or relapsed endometrial cancer, new treatment options have shown a benefit on patients' life expectancy, justifying their update. In first line, the choice will be made between chemotherapy with carboplatin/paclitaxel or hormone therapy with progestin, depending on tumor characteristics (histological type, grade, expression of hormone receptors, rate of progression). In case of a dMMR tumors, the use of immunotherapy within the framework of a therapeutic trial is an option.

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French recommendations for clinical practice Nice-Saint-Paul de Vence 2022-2023: histomolecular diagnosis of endometrial carcinomas The characterisation of endometrial carcinomas has been recently modified and enriched by molecular classification, the integration of which now impacts therapeutic decisions on whether adjuvant therapy should be administered or not in localized tumors, and influences treatment selection in advanced disease. Mandatory information includes histological type according to WHO 2020 classification, histological grade, hormone receptors status and molecular classification, the main new elements to provide being analysis of MMR proteins, p53 status and POLE status in selected cases. Sampling and preparation of material must be performed adequately to allow complete analysis.

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Objective: To describe the patterns of recurrence and the prognosis of patients with a recurrent TP53 mutated endometrial carcinoma treated initially by surgery.

Methods: All patients with endometrial carcinoma, treated at hospital European Georges Pompidou between 2001 and 2021 were retrospectively included. Patients were separated into two groups: TP53-mutated and not TP53-mutated (POLE/ultramutated-like (POLEmut), dMMR (mismatch repair-deficient) and NSMP (No specific molecular profile)).

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Introduction: In early cervical cancer (EEC), 10 to 15% of patients without nodal metastasis (N-) will suffer from recurrences with further similar survival as N+ patients. However, no clinical, imaging or pathological risk-factor is today available to identify them. In the present study, we hypothesized that the N- histologically characterized patients who present a poor prognosis could be patients for whom metastasis are missed by classical procedure.

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Article Synopsis
  • - The study addresses the challenge of distinguishing metastatic cervical cancer from new primary tumors in patients with a history of cervical cancer by utilizing HPV molecular genotyping tests.
  • - Researchers analyzed cases from 2010 to 2020 involving patients with cervical cancer and new lesions, employing a specific PCR method to detect high-risk HPV DNA in those lesions.
  • - The findings showed that in most cases, the presence of HPV DNA confirmed cervical cancer metastasis, while one case revealed no HPV, indicating a new primary lung cancer, thus demonstrating the potential efficacy of molecular genotyping in diagnosis.
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The landscape of uterine sarcomas is becoming increasingly complex with the description of new entities associated with recurrent molecular alterations. Uterine sarcomas, as well as soft tissue sarcomas, can be distinguished into complex genomic sarcomas and simple genomic sarcomas. Leiomyosarcoma and pleomorphic type undifferentiated uterine sarcoma belong to the first group.

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Background: Molecular alterations leading to homologous recombination deficiency (HRD) are heterogeneous. We aimed to identify a transcriptional profile shared by endometrial (UCEC), breast (BRCA) and ovarian (OV) cancers with HRD.

Methods: Genes differentially expressed with HRD genomic score (continuous gHRD score) in UCEC/BRCA/OV were identified using edgeR, and used to train a RNAseq score (ridge-regression model) predictive of the gHRD score (PanCanAtlas, N = 1684 samples).

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The surgical specificities of advanced low-grade serous ovarian carcinoma (LGSOC) have been little investigated. Our objective was to describe surgical procedures/complications in primary (PDS) compared to interval debulking surgery (neoadjuvant chemotherapy and interval debulking surgery, NACT-IDS) and to assess the survival (progression-free (PFS) and overall survival (OS)) in patients with advanced LGSOC. We retrospectively analyzed advanced LGSOC from a nationwide registry (January 2000 to July 2017).

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Background: Despite recent advances in endometrial carcinoma (EC) molecular characterization, its prognostication remains challenging. We aimed to assess whether RNAseq could stratify EC patient prognosis beyond current classification systems.

Methods: A prognostic signature was identified using a LASSO-penalized Cox model trained on TCGA (N = 543 patients).

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Oncogenetic testing is now part of standard management in high grade ovarian cancer, including at least mutational status of BRCA1/BRCA2 genes. If necessary, tumor genetic testing is followed by constitutional testing to either confirm the constitutional origin of variants identified in BRCA1/2 genes or detect variants in other predisposition genes. The whole process including prescription of tumoral testing, retrieval of analysis report and communication of results must be formalized, as well as information on possible consequences of the results for the patient and her family.

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Article Synopsis
  • New molecular therapies have emerged for advanced gynecological cancers, particularly highlighting targeted treatments like PARP inhibitors (PARPi) for high-grade serous ovarian cancers linked to BRCA mutations.
  • Current research indicates that PARPi might also be effective in tumors without BRCA mutations, suggesting potential benefits for advanced endometrial and cervical cancers where treatment options are limited.
  • Although data on the use of PARPi in endometrial and cervical cancers is still scarce, some preliminary results show promise and are discussed in this review.
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Background: Lymphadenectomy is debated in patients with ovarian cancer. The aim of our study was to evaluate the impact of lymphadenectomy in patients with high-grade serous ovarian cancer receiving neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS).

Methods: A retrospective, unicentric study including all patients undergoing NACT and IDS was carried out from 2005 to 2018.

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Article Synopsis
  • - The study investigates the usefulness of CT scans taken before and after neoadjuvant chemotherapy in predicting lymph node involvement in ovarian cancer patients who undergo interval debulking surgery.
  • - Conducted with 158 patients, the research reveals that while the CT scan had low sensitivity and moderate specificity in detecting lymph node positivity, it provides some prognostic information regarding recurrence and overall survival.
  • - The findings suggest that enlarged lymph nodes seen on CT scans are not reliable indicators of actual lymph node involvement, but they could still help gauge patient prognosis in advanced ovarian cancer cases.
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Background: Homologous recombination deficiency is a marker of response to poly(ADP-ribose) polymerase inhibitors in different cancer types including ovary, prostate, and pancreatic cancer. To date, no report about poly(ADP-ribose) polymerase inhibitors has been published on cervical cancer.

Case Presentation: Here we present the case of a patient with cervical cancer treated in this setting.

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Article Synopsis
  • - Endocervical microglandular hyperplasia (MGH) is a benign glandular lesion of the cervix that can resemble endocervical adenocarcinoma in appearances and histological features, making diagnosis difficult.
  • - A proper differential diagnosis is crucial because misidentifying MGH as a malignant condition can lead to unnecessary treatments or anxiety.
  • - The text discusses a case involving a 21-year-old woman who experienced challenges in diagnosis during colposcopy, but was ultimately found to have MGH upon histological examination.
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Endometrial cancer is a common cancer in older women and is often associated with comorbidities. Management of metastatic disease and/or relapse requires a multidisciplinary approach. Recent advances in the understanding of oncogenesis and molecular classification of endometrial cancers offer new therapeutic perspectives.

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Fumarate hydratase (FH)-deficient uterine leiomyomas represent 1% of all uterine leiomyomas. They show distinctive morphology, and are often associated with a loss of expression of FH protein, secondary to the inactivation of the FH gene. They can occur sporadically or in the hereditary setting of hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome associated with germline mutations of FH gene.

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Patients who carry the BReast Cancer 1 or 2 (BRCA) gene mutations have an underlying hereditary predisposition for breast and ovarian cancers. These deleterious genetic mutations are the most common ones implicated in hereditary breast and ovarian cancers. Oncogenetic counselling plays a key role in identifying patient for BRCA testing and for mutation identification.

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Purpose Of Investigation: The objective of this study was to evaluate the best pre- and intra-operative strategy to determine the European Society for Medical Oncology (ESMO) risk group.

Materials And Methods: Retrospective study on patients supported for endometrial cancer between 2006 and 2011. Twelve algorithms, integrating endometrial biopsy for histological type and tumour grade, and ultrasound and/or magnetic resonance imaging (MRI)±intra-operative examination for determination of myometrial invasion, were built.

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Müllerian inhibiting substance, also called anti-Müllerian hormone (AMH), inhibits proliferation and induces apoptosis of AMH type II receptor-positive tumor cells, such as human ovarian cancers (OCs). On this basis, a humanized glyco-engineered monoclonal antibody (3C23K) has been developed. The aim of this study was therefore to experimentally confirm the therapeutic potential of 3C23K in human OCs.

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Lynch syndrome is a hereditary predisposition to many tumors, in the forefront of which endometrial cancer in women. It is related to the mutation of a mismatch repair gene, involved in DNA mismatch repair. This mutation leads to a loss of expression of the corresponding protein, and to genome instability in tumor cells.

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