Sirtuin1 Expression and Correlation with Histopathological Features in Retinoblastoma

Abstract

Background: Sirtuin1 (Sirt1) is a member of highly conserved proteins and has been implicated as a tumor promoter as well as a tumor suppressor. One of the mechanisms involves deacetylation of retinoblastoma protein, thereby inhibiting the tumor suppressor function. No study has been reported on the expression of Sirt1 in retinoblastoma. Methods: We assessed the expression of Sirt1 in sections of archived tissue blocks of enucleated and exenterated specimens of retinoblastoma patients by immunohistochemistry. The histopathological features were reviewed and correlated with the expression of Sirt1. The effect of Sirt1 expression on survival was also assessed. Results: Retrospective data of 94 patients revealed that the median age at presentation was 36 months, with a male:female ratio of 1.9:1. Fifty-one percent of the patients had International Retinoblastoma Staging System (IRSS) stage 1 disease. Of the 94 sections, 89 (95%) expressed Sirt1. Forty-eight percent of the specimens showed grade 3 staining (>75% of the cells), and the intensity was 3+ in 53%. No association between Sirt1 expression and any histopathological feature was noted. Further, Sirt1 expression did not affect the overall and progression-free survival. Conclusions: Sirt1 was expressed in most of the retinoblastoma samples. However, the degree of Sirt1 expression was not associated with any high-risk histopathological feature or survival.

Sirtuin1 expression and survival in endometrial and clear-cell uterine cancer

“…This histone-deacetylase is known to be involved in the pathophysiology of metabolic diseases and neurodegenerative disorders (Lavu et al 2008 ). Regarding cancer progression its role is controversially discussed and is known to differ in respect to tissue and cancer entity: SIRT1 expression does not seem to have any prognostic significance in retinoblastoma (Batra et al 2015 ). In contrast, in adenocarcinoma and small cell carcinoma of the lung, SIRT1 seems to be associated with poor survival, which can also be observed in large B-cell lymphoma and in clear cell renal cell carcinomas (Chen et al 2017 ; Jang et al 2008 ; Noh Baek et al 2013a , b ; Noh Kang et al 2013a , b ; Wang and Wang 2016 ).…”

Histone Deacetylases in Retinoblastoma

“…However, the impact of HDACs on cancer development may not solely hinge on their expression levels, as aberrant HDAC activity is also prevalent in tumorigenesis development [83]. Upregulated expression [90]. Silencing of SIRT1 showed that SIRT1-mediated deacetylation is essential for deactivating Rb [91].…”

“…MYCN proto-oncogene directly stimulates the transcription of SIRT1, enhancing the stability of this oncogenic protein [92] Upregulated expression [90]. Silencing of SIRT1 showed that SIRT1-mediated deacetylation is essential for deactivating Rb [91].…”

“…Upregulated expression [90]. Silencing of SIRT1 showed that SIRT1-mediated deacetylation is essential for deactivating Rb [91].…”

“…MYCN proto-oncogene directly stimulates the transcription of SIRT1, enhancing the stability of this oncogenic protein [92]. Upregulated expression [90]. Silencing of SIRT1 showed that SIRT1-mediated deacetylation is essential for deactivating Rb MYCN proto-oncogene directly stimulates the transcription of SIRT1, enhancing the stability of this oncogenic protein [92] By inducing hyperacetylation of both histone and nonhistone substrates, HDACs can either suppress the expression of tumor suppressor genes or modulate oncogenic signaling pathways by modifying critical molecules.…”