Immunohistochemical expression of TFF1 is a marker of poor prognosis in
retinoblastoma.
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.