Publications by authors named "Just Pierre-Alexandre"

Context.—: A correlation between the morphology of ovarian high-grade serous carcinomas (HGSOCs) and BRCA mutations has been previously reported.

Objective.

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PD-1/PD-L1 blockade has so far shown limited survival benefit for high-grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial (NCT03275506), for which primary outcomes are published, and by combining RNA-seq and multiplexed immunofluorescence staining, we explore the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment, and identify parameters that correlated with response to immunotherapy as a pre-planned exploratory analysis. Indeed, i) combination therapy results in a significant increase in intraepithelial CD8PD-1 T cells, ii) combining endothelial and monocyte gene signatures with the CD8B/FOXP3 expression ratio is predictive of response to NACT + P with an area under the curve of 0.

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Objective: This study aimed to establish the first-ever MRI classification of uterosacral ligament (USL) involvement in deep infiltrating endometriosis (DIE), based on reliable preoperative MRI features correlated with positive predictive values (PPVs) determined through histopathological analysis.

Methods: Twenty-two women underwent surgery with histopathology due to symptoms highly suggestive of endometriosis. The 22 preoperative MRIs were analysed retrospectively, blinded to histopathology, and a classification of the preoperative aspect of USLs linked to PPVs was designed.

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Article Synopsis
  • - The study aimed to validate the SeqOne assay for detecting homologous recombination deficiency (HRD) using tumor samples from the PAOLA-1 trial, comparing it to the Myriad MyChoice HRD test.
  • - Results showed a high concordance rate of 95% between the two tests in determining HRD status, with both assays suggesting significant benefits of olaparib plus bevacizumab treatment for patients with HRD-positive tumors.
  • - The findings indicate that the SeqOne assay is a clinically validated method for detecting HRD, which can help tailor treatment strategies for advanced ovarian cancer patients.
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Homologous recombination deficiency (HRD) is a predictive biomarker for poly(ADP-ribose) polymerase 1 inhibitor (PARPi) sensitivity. Routine HRD testing relies on identifying BRCA mutations, but additional HRD-positive patients can be identified by measuring genomic instability (GI), a consequence of HRD. However, the cost and complexity of available solutions hamper GI testing.

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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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Aims: Struma ovarii (SO) are rare, accounting for 0.3-1% of ovarian tumours, and include benign and malignant lesions. In most cases, histology is not predictive of clinical outcome and prognosis.

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Renal cell carcinoma (RCC) with rearrangement of transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3; TFE3-rearranged RCC) at Xp11.2 is a rare tumor entity but the most frequent among the microphthalmia transcription factor family translocation RCCs. Here, we report the identification of a new VCP::TFE3 fusion gene as the result of a t(X;9)(p11.

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Objective: To identify circulating miRNAs associated with ovarian endometriosis (OMA), and to analyze candidate genes targeted by these miRNAs. Methods: Putative regulating miRNAs were identified through an original bioinformatics approach. We first queried the miRWalk 2.

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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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Introduction: Adjuvant therapeutic decisions in older endometrial carcinoma (EC) patients are challenged by a balance between more frequent aggressive EC and comorbidities. We assessed whether EC and comorbidities are competing or cumulative risks in older EC patients.

Methods: All consecutive patients treated for FIGO stage I-IV EC in two University Hospitals in Paris between 2010 and 2017 were retrospectively included.

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Background: No circulating biomarker is available for endometrial carcinoma (EC). We aimed to identify DNA positions universally hypermethylated in EC, and to develop a digital droplet PCR (ddPCR) assay for detection of hypermethylated circulating tumor DNA (meth-ctDNA) in plasma from patients with EC.

Methods: DNA positions hypermethylated in EC, and without unspecific hypermethylation in tissue/cell types releasing circulating cell-free DNA in plasma, were identified in silico from TCGA/Gene Expression Omnibus (GEO) data.

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Background: There are limited treatment options for ovarian cancer patients with early relapse after platinum chemotherapy. In preclinical studies, we previously demonstrated the promising activity of ABT-737, a Bcl-2/Bcl-x anti-apoptotic protein inhibitor, in chemo-resistant ovarian cancer cells and tumors, suggesting its potential activity in platinum-resistant patients.

Methods: We conducted a prospective multicenter single-arm phase II study to assess the efficacy of Navitoclax (orally available ABT-737 analogue) monotherapy in 46 heavily pretreated (2-12 lines, median = 4) patients with high-grade serous platinum-resistant ovarian tumors.

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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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Article Synopsis
  • HPRCC is a rare genetic condition leading to multiple tumors primarily of papillary renal cell carcinoma due to mutations in the MET gene, with no previously reported clear cell RCC cases.
  • A 51-year-old man with a MET mutation developed both papillary and unexpected clear cell RCCs, which later metastasized to the adrenal gland.
  • The findings suggest a potential link between papillary and clear cell RCCs in HPRCC, indicating that pathologists should conduct comprehensive genomic analyses when faced with unusual tumor presentations in such cases.
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The accurate diagnosis of Xp11-translocation renal cell carcinoma (RCC) in adults is challenging. TFE3 (located on chromosome X) fuses with a partner gene generally located on another chromosome. In rare cases TFE3 may fuse with a neighboring gene: RBM10.

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The treatment of endometrial carcinomas relies on histopathological data such as tumor type, grade, stage, and lymphovascular invasion. We herein present the recent advances in the pathological appreciation of these criteria, relying in the last 2020 WHO classification of female genital tumours. Furthermore, molecular typing of endometrial carcinoma has become a rule with strong prognostic and therapeutic implications.

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Purpose: To make clear distinction between two radiological types of uterine sarcomas.

Methods: 50 preoperative MRI were analyzed retrospectively, blinded to histopathology: 11 endometrial stromal sarcomas (ESS), 19 leiomyosarcomas (LMS), 18 carcinosarcomas/malignant mixed Mullerian tumors (MMMT), and 2 smooth muscle tumors of uncertain malignant potential (STUMP).

Results: According to their locations, two radiological types of sarcomas were identified: type 1: intracavitary (ESS, MMMT) and type 2: intramyometrial (LMS, STUMP).

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Diffuse adenomyosis, focal adenomyosis, ovarian endometrioma, superficial endometriosis and deep infiltrating adenomyosis are all defined by the presence of an endometrioid tissue in an ectopic location that is at distance from the endometrium. Although frequently associated, these lesions represent different clinico-pathological entities that the pathologist should recognized. Herein, we review the clinical and pathological features of these entities, as well as related current physiopathological understandings and differential diagnoses that could be raised by some morphological variants.

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Background: PAOLA1 is a phase III study assessing olaparib maintenance therapy in advanced high-grade ovarian carcinoma patients responding to first-line platinum-taxane-based chemotherapy plus bevacizumab as standard of care. Randomization was stratified by treatment outcome and tumor BRCA1/2 status (tBRCA) at screening.

Methods: tBRCA was tested on formalin-fixed, paraffin-embedded tumor blocks on 5 French platforms using 2 next-generation sequencing methods based either on hybrid capture or amplicon technology.

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