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\begin{document}

\title{Immunohistochemical expression of TFF1 is a marker of poor prognosis in
retinoblastoma.}



\author[1]{Rosario Aschero}%
\author[2]{Daiana Ganiewich}%
\author[1]{Gabriela Lamas}%
\author[3]{Camilo Restrepo-Perdomo A}%
\author[4]{Daniela Ottaviani}%
\author[1]{Santiago Zugbi}%
\author[1]{Sandra Camarero}%
\author[1]{Ezequiel Néspoli}%
\author[3]{Maria Cuadrado Vilanova}%
\author[3]{Sara Perez-Jaume}%
\author[3]{Guillem Pascual-Pasto}%
\author[5]{Claudia Sampor}%
\author[6]{Nathalia Grigorovski}%
\author[7]{Beatriz Salas}%
\author[3]{Mariona Suñol}%
\author[3]{Angel M. Carcaboso}%
\author[3]{Jaume Mora}%
\author[1]{Maria TG de Davila}%
\author[4]{Francois Doz}%
\author[4]{Francois Radvanyi}%
\author[8]{David Abramson}%
\author[9]{Andrea Llera S}%
\author[1]{Paula Schaiquevich}%
\author[1]{Fabiana Lubieniecki}%
\author[9]{Guillermo Chantada}%
\affil[1]{Hospital de Pediatria Prof Dr Juan P Garrahan}%
\affil[2]{Universidad Austral Facultad de Ciencias Biomedicas}%
\affil[3]{Hospital Sant Joan de Deu}%
\affil[4]{Institut Curie}%
\affil[5]{Hospital de Pediatria Prof Dr Juan P Garrahan Servicio de Hematologia y Oncologia}%
\affil[6]{Instituto Nacional de Cancer}%
\affil[7]{Hospital del Nino Manuel Ascencio Villarroel}%
\affil[8]{Memorial Sloan Kettering Cancer Center}%
\affil[9]{Consejo Nacional de Investigaciones Cientificas y Tecnicas}%


\vspace{-1em}



  
  \date{May 18, 2024}


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\begin{abstract}
\textbf{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. \textbf{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 \textgreater{} 50).
We studied the association between HS classification and outcome.
\textbf{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 ( \emph{P} \textless{} 0.0001 and \emph{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 ( \emph{P} = 0.012 and \emph{P} = 0.027,
respectively). \textbf{Conclusions}: Expression of TFF1, especially when
it is not-mutually exclusive with ARR3, is an independent prognostic
marker of poor outcome in retinoblastoma.%
\end{abstract}%



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\verb`Manuscript file.docx`  available at \url{https://authorea.com/users/644626/articles/657462-immunohistochemical-expression-of-tff1-is-a-marker-of-poor-prognosis-in-retinoblastoma}\selectlanguage{english}
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\verb`Table 1.docx`  available at \url{https://authorea.com/users/644626/articles/657462-immunohistochemical-expression-of-tff1-is-a-marker-of-poor-prognosis-in-retinoblastoma}

\textbf{Hosted file}

\verb`Table 2.docx`  available at \url{https://authorea.com/users/644626/articles/657462-immunohistochemical-expression-of-tff1-is-a-marker-of-poor-prognosis-in-retinoblastoma}

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\verb`Table 3.docx`  available at \url{https://authorea.com/users/644626/articles/657462-immunohistochemical-expression-of-tff1-is-a-marker-of-poor-prognosis-in-retinoblastoma}

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