Trefoil Family Factor 1 Expression in the Indian Cohort of Treatment-Naïve Retinoblastoma.

Introduction: Retinoblastoma (RB) is the most common intraocular malignancy of childhood. Advanced RB has a poor prognosis and is associated with high-risk histopathological factors (HRPFs), metastasis, and relapse. Trefoil family factor 1 (TFF1), a secreted peptide previously associated with adverse clinicopathological features in RB, has emerged as a potential biomarker of aggressive disease; however, its clinical significance in Indian patients remains poorly understood. This study evaluated TFF1 expression in correlation with HRPFs, metastasis, and survival outcomes. Methods: This study included 40 treatment-naïve patients with RB who underwent primary enucleation as their initial management at a tertiary ocular oncology center. Immunohistochemistry was performed to assess TFF1 expression, which was quantified using a quick score (QS) ranging from 0 to 300, based on staining intensity and percentage of positive cells. Tumors were classified into low-expression (HS1; QS < 50) groups and high-expression (HS2; QS ≥ 50) groups. Associations between QS and high-risk pathological features, metastasis, and survival outcomes were analyzed. Results: Among 40 patients, 45% were classified as HS2 and 55% as HS1. HRPFs were identified in 55% (22/40) of cases. HRPF positivity was more frequently observed in HS2 tumors (57.1%) than HS1 tumors (42.9%), although the difference did not reach statistical significance ( Conclusion: Higher TFF1 expression was associated with high-risk factors, including massive choroidal invasion, post-laminar optic nerve invasion, metastasis, recurrence, and disease-related mortality. Although these associations did not reach statistical significance, the observed trends suggest that TFF1 may contribute to the biological stratification of RB and warrant further evaluation in larger cohorts.