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Clinical, pathological, and comprehensive molecular analysis of the uterine clear cell carcinoma: a retrospective national study from TMRG and GINECO network.
Nigon, Elsa; Lefeuvre-Plesse, Claudia; Martinez, Alejandra; Chauleur, Céline; Lortholary, Alain; Favier, Laure; Bats, Anne-Sophie; Guille, Arnaud; AdélaÏde, José; Finetti, Pascal; de Casteljac, Victoire; Provansal, Magali; Mamessier, Emilie; Bertucci, François; Ray-Coquard, Isabelle; Sabatier, Renaud.
Afiliação
  • Nigon E; Department of Medical Oncology, Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, Marseille, France.
  • Lefeuvre-Plesse C; Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
  • Martinez A; Department of Surgical Oncology, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France.
  • Chauleur C; Department of Medical Oncology, Institut de Cancérologie de la Loire, Saint Etienne, France.
  • Lortholary A; Hôpital privé du Confluent, Institut de Cancérologie Catherine de Sienne, Nantes, France.
  • Favier L; Department of Medical Oncology, Centre Georges-François Leclerc, Dijon, France.
  • Bats AS; Department of Surgical Oncology, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France.
  • Guille A; CRCM, Predictive Oncology laboratory, Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, Marseille, France.
  • AdélaÏde J; CRCM, Predictive Oncology laboratory, Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, Marseille, France.
  • Finetti P; CRCM, Predictive Oncology laboratory, Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, Marseille, France.
  • de Casteljac V; Department of Medical Oncology, Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, Marseille, France.
  • Provansal M; Department of Medical Oncology, Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, Marseille, France.
  • Mamessier E; CRCM, Predictive Oncology laboratory, Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, Marseille, France.
  • Bertucci F; Department of Medical Oncology, Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, Marseille, France.
  • Ray-Coquard I; CRCM, Predictive Oncology laboratory, Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, Marseille, France.
  • Sabatier R; Department of Medical Oncology, Centre Léon Bérard, University Claude Bernard Lyon 1, Lyon, France.
J Transl Med ; 21(1): 408, 2023 06 23.
Article em En | MEDLINE | ID: mdl-37353806
BACKGROUND: Uterine clear cell carcinomas (CCC) represent less than 5% of uterine cancers. Their biological characteristics and clinical management remain uncertain. A multicenter study to explore both clinical and molecular features of these rare tumors was conducted. METHODS: This multicenter retrospective national study was performed within the French TMRG (Rare Gynecologic Malignant Tumors) network. Clinical data and, when available, FFPE blocks were collected. Clinical features, treatments, and outcome (progression-free survival (PFS) and overall survival (OS)) were analyzed and correlated to the protein (tissue micro-array), RNA (Nanostring nCounter® technology), and DNA (array-Comparative Genomic hybridization and target-next generation sequencing) levels using the tumor samples available. RESULTS: Sixty-eight patients with uterine CCC were enrolled, 61 from endometrial localization and 5 with cervix localization. Median age at diagnosis was 68.9 years old (range 19-89.7). Most tumors were diagnosed at an early stage (78% FIGO stage I-II). Hysterectomy (performed in 90%) and lymph node dissection (80%) were the most frequent surgical treatment. More than 70% of patients received external beam radiotherapy and 57% received brachytherapy. Nearly half (46%) of the patients received chemotherapy. After a median follow-up of 24.7 months, median PFS was 64.8 months (95 CI [5.3-124.4]) and median OS was 79.7 (IC95 [31.0-128.4]). Low hormone receptor expression (13% estrogen-receptor positive), frequent PI3K pathway alterations (58% PTEN loss, 50% PIK3CA mutations), and P53 abnormalities (41%) were observed. Mismatch repair deficiency was identified in 20%. P16 expression was associated with shorter PFS (HR = 5.88, 95 CI [1.56-25], p = 0.009). Transcriptomic analyzes revealed a specific transcriptomic profile notably with a high expression of immune response-associated genes in uterine CCC displaying a very good overall prognosis. CONCLUSIONS: Uterine CCC reported to be potentially MSI high, hormone receptors negative, and sometimes TP53 mutated. However, some patients with immune response-associated features and better prognosis may be candidate to treatment de-escalation and immunotherapy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Uterinas / Carcinoma Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Uterinas / Carcinoma Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Ano de publicação: 2023 Tipo de documento: Article