Published October 30, 2023 | Version v1
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TP53 mutations are associated with improved survival in ovarian carcinoma patients receiving first-line chemotherapy plus bevacizumab: results from the MITO16A/MaNGO OV-2 study

Authors/Creators

  • 1. Angelo Nocivelli' Institute of Molecular Medicine, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy; Division of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, Brescia, Italy
  • 2. Department of Mental Health and Public Medicine, Section of Statistics, Università Degli Studi Della Campania Luigi Vanvitelli, 80138 Naples, Italy
  • 3. Department of Pathology, ASST Spedali Civili di Brescia, Brescia, Italy
  • 4. Department of Biomedical Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pathology Unit, 20122 Milan, Italy
  • 5. IRCCS Humanitas Research Hospital, Molecular Pharmacology Lab, Rozzano, Italy
  • 6. Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori IRCCS, Fondazione G. Pascale, 80131 Naples, Italy
  • 7. Uro-Gynecological Medical Oncology, Istituto Nazionale Tumori, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione G Pascale, Naples, Italy.
  • 8. Pathology Unit, Istituto Nazionale Tumori IRCCS, Fondazione G. Pascale, 80131 Naples, Italy.
  • 9. Clinical Trials Unit, Istituto Nazionale Tumori IRCCS, Fondazione G. Pascale, 80131 Naples, Italy
  • 10. Division of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, Brescia, Italy
  • 11. Department of Life Science and Public Health, Catholic University of Sacred Heart Largo Agostino Gemelli, and Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
  • 12. Division of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, Brescia, Italy ; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
  • 13. Oncologia Medica, Ospedali Galliera, Genoa, Italy

Description

PURPOSE Bevacizumab (BEV) is considered an effective treatment option for advanced ovarian carcinoma. However, to date, there are no biomarkers that define a BEV-responsive patient subpopulation.

METHODS In the context of the MITO16A/MaNGO OV-2 trial, a phase IV study of chemotherapy combined with BEV in first-line treatment of advanced ovarian carcinoma, we evaluated TP53 mutations by next generation sequencing (NGS) and p53 protein expression by immunohistochemistry (IHC) on 202 and 311 cases, respectively. We further correlated NGS and IHC data with clinicopathological characteristics and survival of patients.

RESULTS TP53 mutations of unknown function (named unclassified), mostly of the missense type, represented the majority of variants in our population (44.4%) and were associated with a significantly improved overall survival both in univariate (p=0.03, HR=0.43) and multivariate analysis (p=0.012, HR=0.39). Concordance between TP53 mutational analysis and protein expression was 91%. A trend toward improved OS was observed in patients with p53 IHC overexpression (HR=0.70, p=0.15) compared to p53 wild-type patients.

CONCLUSION Our results indicate that the presence of unclassified TP53 mutations has favorable prognostic significance in patients with ovarian carcinoma receiving upfront BEV plus chemotherapy. In particular, unclassified missense TP53 mutations characterize a subpopulation of patients with a significant survival advantage, independently of clinicopathological characteristics. Our findings warrant future investigations to confirm the prognostic impact of TP53 mutations in BEV-treated ovarian carcinoma patients and deserve to be assessed for their potential predictive role in future randomized clinical studies.

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