Analysis of A Disintegrin and Metalloprotease 17 (ADAM17) Expression as a Prognostic Marker in Ovarian Cancer Patients Undergoing First-Line Treatment Plus Bevacizumab.

ADAM17 bevacizumab treatment immunohistochemistry ovarian cancer prognostic biomarker

Journal

Diagnostics (Basel, Switzerland)
ISSN: 2075-4418
Titre abrégé: Diagnostics (Basel)
Pays: Switzerland
ID NLM: 101658402

Informations de publication

Date de publication:
31 Aug 2022
Historique:
received: 18 07 2022
revised: 20 08 2022
accepted: 29 08 2022
entrez: 23 9 2022
pubmed: 24 9 2022
medline: 24 9 2022
Statut: epublish

Résumé

To find prognostic factors for advanced ovarian cancer patients undergoing first-line therapy with carboplatin, paclitaxel and bevacizumab, we investigated the expression of a disintegrin and metalloprotease 17 (ADAM17) in cancer tissues. ADAM17 has been involved in ovarian cancer development, progression and cell resistance to cisplatin. Tissue microarrays from 309 ovarian cancer patients enrolled in the MITO16A/MANGO-OV2 clinical trial were analyzed by immunohistochemistry for ADAM17 protein expression. Intensity and extent of staining were combined into a semi-quantitative visual grading system (H score) which was related to clinicopathological characteristics of cases and the clinical outcome of patients by univariate and multivariate Cox regression models. ADAM17 immunostaining was detected in most samples, mainly localized in the tumor cells, with variable intensity across the cohort. Kaplan-Meier survival curves, generated according to the best cut-off value for the ADAM17 H score, showed that high ADAM17 expression was associated with worse prognosis for PFS and OS. However, after the application of a shrinkage procedure to adjust for overfitting hazard ratio estimates, the ADAM17 value as prognostic factor was lost. As subgroup analysis suggested that ADAM17 expression could be prognostically relevant in cases with no residual disease at baseline, further studies in this patient category may be worth planning.

Identifiants

pubmed: 36140519
pii: diagnostics12092118
doi: 10.3390/diagnostics12092118
pmc: PMC9498026
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Italian Association for Cancer Research
ID : IG 5776
Organisme : Italian Ministry of Health
ID : Ricerca Corrente and 5x1000 Funds
Organisme : Associazione Italiana Di Oncologia Medica
ID : To S.P.

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Auteurs

Marina Fabbi (M)

UO Bioterapie, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.

Delfina Costa (D)

UO Oncologia Molecolare e Angiogenesi, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.

Daniela Russo (D)

Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Laura Arenare (L)

Clinical Trials Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Gabriele Gaggero (G)

UO Anatomia Patologica Ospedaliera, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.

Simona Signoriello (S)

Department of Mental Health and Public Medicine, Section of Statistics, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy.

Giovanni Scambia (G)

Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Department of Life Science and Public Health, Catholic University of Sacred Heart, Largo Agostino Gemelli, 00168 Rome, Italy.

Carmela Pisano (C)

Urogynecological Medical Oncology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Nicoletta Colombo (N)

European Institute of Oncology IRCCS, University of Milan-Bicocca, 20126 Milan, Italy.

Nunzia Simona Losito (NS)

Pathology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Gilberto Filaci (G)

UO Bioterapie, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.

Anna Spina (A)

Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Daniela Califano (D)

Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Giosuè Scognamiglio (G)

Pathology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Angiolo Gadducci (A)

Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, 56127 Pisa, Italy.

Delia Mezzanzanica (D)

Molecular Therapies Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.

Marina Bagnoli (M)

Molecular Therapies Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.

Silvano Ferrini (S)

UO Bioterapie, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.

Vincenzo Canzonieri (V)

Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.
Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy.

Paolo Chiodini (P)

Department of Mental Health and Public Medicine, Section of Statistics, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy.

Francesco Perrone (F)

Clinical Trials Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Sandro Pignata (S)

Urogynecological Medical Oncology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Classifications MeSH