Expression of Ki67 as detected by MIB-1 and its association with histopathological high-risk factors among patients with retinoblastoma tumour: a cross-sectional study

Abstract

ObjectivesThis study aims to investigate the expression of Ki67 in formalin-fixed paraffin-embedded tissue blocks from patients with a diagnosis of retinoblastoma tumour (RbT) as well as determining its association with histopathological high-risk factors (HHRFs).Methods and analysisRetrospectively, a total of 194 eyeball specimens from 163 children with RbT were reviewed at Muhimbili National Hospital between 2009 and 2013. Immunohistochemical expression of Ki67 using MIB-1 antibody (Abcam, batch ab93680, Cambridge, UK) was determined and correlated with the conventional HHRFs. The predictors of Ki67 expression were determined using binary logistic regression model in multivariate analysis. A two-tailed p<0.05 was considered statistically significant.ResultsMajority (67.5%) of the patients had leukocoria and extraocular disease was found in 20.9% of all the patients. High expression of Ki67 was present in 63.8% of the 80 eyeballs that were tested. Massive choroidal invasion (adjusted OR (AOR)=9.32, 95% CI=2.82 to 10.89), positive retrolaminar optic nerve invasion (AOR=3.01, 95% CI=4.43 to 9.11), positive surgical margin (AOR=7.10, 95% CI=1.63 to 11.40) and pT4 (AOR=7.49, 95% CI=0.12 to 0.89) were the potential HHRFs that were associated with Ki67 overexpression.ConclusionOverexpression of Ki67 may be of prognostic value for patients with RbT as it has been shown in the present study that high expression was common in tumours with massive choroidal invasion, positive retrolaminar optic nerve invasion, positive surgical margin and advanced tumour stage, which are the conventional HHRFs associated with prognosis of RbT.

Translational screening platform to evaluate chemotherapy in combination with focal therapy for retinoblastoma

“…As expected, the proliferative activity (Ki-67) was high, notably in the outer proliferative rim for Y79 tumoroids. 33 Furthermore, the retinoblastoma tumoroids maintained both nuclear expression of early photoreceptor/cone marker orthodenticle homeobox 2 (OTX1-2) and cytoplasmic expression of late cone marker arrestin 3 (ARR3), which would define Y79 and WERI-Rb1 2D and 3D as subtype 2 retinoblastoma, following the classification of Liu et al 34 The Y79 tumoroids did not show significant differences in marker gene expression compared to 2D culture when analyzed at the RNA level (Figure S5). The only noticeable difference, although not significant, is a tendency to upregulate the pro-apoptotic factor BNIP3, linked to hypoxia, which might indicate the presence of a hypoxic region in the tumoroid model.…”

“…As expected, the proliferative activity (Ki‐67) was high, notably in the outer proliferative rim for Y79 tumoroids. 33 Furthermore, the retinoblastoma tumoroids maintained both nuclear expression of early photoreceptor/cone marker orthodenticle homeobox 2 (OTX1‐2) and cytoplasmic expression of late cone marker arrestin 3 (ARR3), which would define Y79 and WERI‐Rb1 2D and 3D as subtype 2 retinoblastoma, following the classification of Liu et al 34 …”