Telomerase reverse transcriptase catalytic subunit expression and proliferation index in Wilms tumor

Abstract

Telomerase activity provides telomere maintenance in chromosomes. It prevents cells from entering senescence. Telomerase activity is one of the crucial steps in various cancers. Wilms tumor (nephroblastoma) is one of the most common solid tumors of childhood. Hitherto, telomerase reverse transcriptase (TERT) catalytic subunit expression in Wilms tumor has not been investigated widely. The aim of this study was to explore the expression level of human TERT in Wilms tumor and to correlate with some clinical prognosis factors such as tumor weight, stage, histology, and Ki67 expression. This study included 41 nephroblastoma cases of childhood. The telomerase catalytic subunit expression and proliferation index was determined using an immunohistochemical method on archival paraffin-embedded tissue sections. Statistical analysis was done on SPSS 9.05 by Mann-Whitney U test and Spearman's correlation analysis. TERT expression was negative in 11 cases (26.8%), weakly positive in 14 cases (34.1%), and strongly positive in 16 cases (39%). The proliferation index was found to be 20 to 90 (mean 58.9 ± 26.8). Using Spearman correlation analysis, both the TERT expression (p=0.032) and Ki67 index (p=0.048) were found to be correlated with survival rate. Similarly, both the telomerase expression (p=0.011) and the Ki67 index (0.040) were correlated with the weight and dimension of the tumor. But there was no relationship between telomerase expression and Ki67 index (p=0.429). The mean survival time for telomerase negative cases was 56.6 ± 27.3 months, while it was 34.67 ± 28.36 months for positive cases. The Mann-Whitney U test revealed that levels of telomerase (p=0.040) significantly affected the survival rate. In the present study, we showed that the presence of TERT expression correlated with both tumor size and survival time. These findings suggest that senescence may play an important role in WT evolution, and determination of telomere maintenance will be useful to predict survival and follow-up of patients with Wilms tumor.

Role of expression of p53 and Ki67 in the progression of Wilms tumor; correlation with survival

“…Several studies reported that ki67 positivity is associated with higher tumor stage: like the results of the present study (Juszkiewicz, 1997;Das et al, 2012;Krishna et al, 2016). Moreover, our study proved a positive relation between increased ki67 positivity and shorter disease-free survival and overall survival which is reported also by other studies (Ghanem et al, 2005;Diniz et al, 2011). However, Jurić et al reported that Ki-67 is a relevant marker for assessing the proliferative activity and tumor cell dynamics of nephroblastoma, but it may not be a good clinical prognostic marker (Jurić et al, 2010).…”

Caveolin-1 Expression is Associated with Tumor Size and Therapy Response in Wilms Tumor

“…In most reports, the lowest proliferation index was determined in the stromal component and this component generally survived after chemotherapy. 7,9,10 In the present study, we determined Cav-1 expressions confined the mesenchymal component of WTs with or without perivascular expression in the most cases. The importance of Cav-1 expression is novel and potentially relevant in WT progression, since WT1 has been identified as a suppressor of K-RAS oncogene.…”

“…[5][6][7] Hitherto, many parameters were suggested as relevant markers for assessing the proliferative activity and tumor cell dynamics of the WT. [6][7][8][9] But the presence of Cav-1 expression in WT has not been investigated widely. The aim of this study was both to explore the importance of Cav-1 expression in Wilms tumor and also investigate the relationships between them, and some clinical prognostic factors such as tumor size, stage and histological features.…”

Adult Wilms Tumor

“…Interestingly, 2 of our combined Wilms tumor-metanephric adenoma cases had TERT promoter mutations limited to the Wilms tumor component. High telomerase RNA expression has been associated with poor prognoses in Wilms tumor, 62 and TERT promoter mutations are thought to synergize with BRAF alterations in thyroid cancer to promote an aggressive phenotype. 63 Correlating with these findings, we did find shortening of telomeres in the Wilms tumors associated with these secondary TERT promoter mutations as well as in the metanephric adenoma components.…”