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 < .0001 and p = .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 with tumors that displayed mutually exclusive expression (p = .012 and p = .027, respectively).

Conclusions: Expression of TFF1, especially when it is not-mutually exclusive with ARR3, is an independent significant marker of poor outcome in retinoblastoma.

Keywords: TFF1 expression; high-risk retinoblastoma; histological subtypes; metastatic retinoblastoma; prognostic marker; subtypes classification.