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Immunohistochemical expression of TFF1 is a marker of poor prognosis in retinoblastoma.
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  • Rosario Aschero,
  • Daiana Ganiewich,
  • Gabriela Lamas,
  • Camilo Restrepo-Perdomo A,
  • Daniela Ottaviani,
  • Santiago Zugbi,
  • Sandra Camarero,
  • Ezequiel Néspoli,
  • Maria Cuadrado Vilanova,
  • Sara Perez-Jaume,
  • Guillem Pascual-Pasto,
  • Claudia Sampor,
  • Nathalia Grigorovski,
  • Beatriz Salas,
  • Mariona Suñol,
  • Angel M. Carcaboso,
  • Jaume Mora,
  • Maria TG de Davila,
  • Francois Doz,
  • Francois Radvanyi,
  • David Abramson,
  • Andrea Llera S,
  • Paula Schaiquevich,
  • Fabiana Lubieniecki,
  • Guillermo Chantada
Rosario Aschero
Hospital de Pediatria Prof Dr Juan P Garrahan
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Daiana Ganiewich
Universidad Austral Facultad de Ciencias Biomedicas
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Gabriela Lamas
Hospital de Pediatria Prof Dr Juan P Garrahan
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Camilo Restrepo-Perdomo A
Hospital Sant Joan de Deu
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Daniela Ottaviani
Institut Curie
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Santiago Zugbi
Hospital de Pediatria Prof Dr Juan P Garrahan
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Sandra Camarero
Hospital de Pediatria Prof Dr Juan P Garrahan
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Ezequiel Néspoli
Hospital de Pediatria Prof Dr Juan P Garrahan
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Maria Cuadrado Vilanova
Hospital Sant Joan de Deu
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Sara Perez-Jaume
Hospital Sant Joan de Deu
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Guillem Pascual-Pasto
Hospital Sant Joan de Deu
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Claudia Sampor
Hospital de Pediatria Prof Dr Juan P Garrahan Servicio de Hematologia y Oncologia
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Nathalia Grigorovski
Instituto Nacional de Cancer
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Beatriz Salas
Hospital del Nino Manuel Ascencio Villarroel
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Mariona Suñol
Hospital Sant Joan de Deu
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Angel M. Carcaboso
Hospital Sant Joan de Deu
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Jaume Mora
Hospital Sant Joan de Deu
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Maria TG de Davila
Hospital de Pediatria Prof Dr Juan P Garrahan
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Francois Doz
Institut Curie
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Francois Radvanyi
Institut Curie
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David Abramson
Memorial Sloan Kettering Cancer Center
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Andrea Llera S
Consejo Nacional de Investigaciones Cientificas y Tecnicas
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Paula Schaiquevich
Hospital de Pediatria Prof Dr Juan P Garrahan
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Fabiana Lubieniecki
Hospital de Pediatria Prof Dr Juan P Garrahan
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Guillermo Chantada
Consejo Nacional de Investigaciones Cientificas y Tecnicas

Corresponding Author:guillermoluis.chantada@sjd.es

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Abstract

Introduction: The risk of relapse in retinoblastoma is currently determined by the presence of high-risk histopathologic factors in the enucleated eye. However, the probability of developing metastatic disease is heterogeneous among these patients. Evaluating a biological marker to identify high-risk patients could be useful in clinical setting. This study aims to evaluate whether the expression of TFF1, a surrogate for subtype 2 retinoblastoma, is a prognostic marker for relapse and death. Methods: This multicenter cohort study included 273 patients, 48 of whom had extraocular disease. Immunohistochemical staining were performed for CRX, ARR3, TFF1 and Ki67. Tumors were classified as histological subtype 1 (HS1) if they had low or no expression of TFF1 (quick score (QS) ≤ 50) and as histological subtype 2 (HS2) if they expressed TFF1 diffusely (QS > 50). We studied the association between HS classification and outcome. Results: Of 273 patients, 35.9% were classified as HS1, 59.3% as HS2 and 4.8% were not evaluable. In multivariate analysis, patients with HS2 tumors had a higher probability of relapse and death than those with HS1 ( P < 0.0001 and P = 0.00020, respectively). We identified a higher-risk subgroup among HS2 tumors, presenting non-mutually exclusive expression of ARR3 and TFF1 and had an increased risk of relapse and death compared to tumors that displayed mutually exclusive expression ( P = 0.012 and P = 0.027, respectively). Conclusions: Expression of TFF1, especially when it is not-mutually exclusive with ARR3, is an independent prognostic marker of poor outcome in retinoblastoma.
27 Jul 2023Submission Checks Completed
27 Jul 2023Assigned to Editor
27 Jul 2023Submitted to Pediatric Blood & Cancer
31 Jul 2023Review(s) Completed, Editorial Evaluation Pending
04 Aug 2023Reviewer(s) Assigned
22 Sep 2023Editorial Decision: Revise Minor
28 Sep 2023Submission Checks Completed
28 Sep 2023Assigned to Editor
28 Sep 20231st Revision Received
28 Sep 2023Review(s) Completed, Editorial Evaluation Pending
29 Sep 2023Editorial Decision: Accept