Expression of SIRT2 and SIRT6 in Retinoblastoma

Orellana, María Eugenia; Quezada, Carlos; Maloney, Shawn C.; Antecka, E.; Balazsi, Matthew; Burnier, Miguel N.

doi:10.1159/000368718

Cited by 10 publications

(8 citation statements)

References 37 publications

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“…Although one study demonstrated HDAC1, 2, 3, 5, 6 and 7 proteins in human retinal supernatant via mass spectrometry [37] and another study demonstrated SIRT2 in the inner and outer nuclear and plexiform layers and nerve fibre layer [25], we did not note consistent HDAC1 staining in the retina, instead noting widespread staining of HDAC4 and SIRT2 followed by HDACs 2, 3 and 6.…”

Section: Discussioncontrasting

confidence: 95%

“…SIRT2 has also been detected in the non-pigmented ciliary body epithelium [25], but this was not noted in this study.…”

Section: Discussioncontrasting

confidence: 75%

“…Since HDACs are a diverse group of proteins, we hypothesise that a better understanding of the expression of specific HDACs in human uveal melanoma tissue will lead to a more nuanced and targeted understanding of the roles they play in this devastating disease. Herewith we present immunohistochemical data on the expression of six HDACs (HDAC1, HDAC2, HDAC3, HDAC4, HDAC6 and SIRT2), chosen for their known association with prognosis, grade and stage in other malignancies [13,24,25].…”

Section: Introductionmentioning

confidence: 99%

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Tumour Expression of Histone Deacetylases in Uveal Melanoma

et al. 2018

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Purpose: To determine the expression of histone deacetylase enzymes in uveal melanoma tumour cells. Procedures: This is an observational immunohistochemical study of 16 formalin-fixed, paraffin-embedded eyes enucleated for uveal melanoma between January 2001 and March 2002. Haematoxylin and eosin paraffin sections were reviewed for histopathological parameters according to the American Joint Committee on Cancer 7th edition. Sections were then immunohistochemically stained for histone deacetylases 1, 2, 3, 4 and 6 and sirtuin 2 using an automated Leica Bond II platform and Fast Red chromogen, then digitally scanned using Aperio software before assessment of staining. Results: Nuclear expression of histone deacetylases 1, 2, 3, 4 and 6 and of sirtuin 2 was confirmed in uveal melanoma tumour cells. In addition, the tumour cells showed cytoplasmic expression of histone deacetylases 4 and 6 and sirtuin 2. Nuclear and cytoplasmic immunostaining was also seen in intraocular tissues uninvolved by the tumour. Conclusion: Uveal melanoma tumour cells express histone deacetylases 1, 2, 3, 4 and 6 and sirtuin 2, confirming potential tissue targets for histone deacetylase inhibitors.

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Section: Discussioncontrasting

confidence: 95%

“…SIRT2 has also been detected in the non-pigmented ciliary body epithelium [25], but this was not noted in this study.…”

Section: Discussioncontrasting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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Tumour Expression of Histone Deacetylases in Uveal Melanoma

et al. 2018

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“…Sirt2 and Sirt6 have recently been reported to be expressed in all 18 retinoblastoma blocks with varying intensity [24]. This study along with our study points to the functional relation between Sirt proteins and retinoblastoma and requires future functional studies.…”

Section: Discussionsupporting

confidence: 61%

Sirtuin1 Expression and Correlation with Histopathological Features in Retinoblastoma

et al. 2015

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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.

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“…Conclusions: Overall, [6][7][8] . New treatment options are being developed to target specific RB genes and receptors, thus circumventing some of these potential safety issues [9,10] .…”

Section: Introductionmentioning

confidence: 99%

HER2 Overexpression in Retinoblastoma: A Potential Therapeutic Target

et al. 2017

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Background: Retinoblastoma (RB) is the most common primary intraocular malignancy. Current therapies are associated with high morbidity in the short- and long-term. Human epidermal growth factor receptor 2 (HER2) is a transmembrane protein detected in 15-30% of breast cancers, but it has also been described in other malignancies. Recently, it has been claimed that a truncated version of this protein is expressed in RB, responsive to directed therapies in vitro. We scored HER2 overexpression in RB tissue samples and discussed its potential clinical utility. Methods: HER2 overexpression was investigated using immunohistochemistry; the overexpression was evaluated with a score ranging from 0 to 3+ according to the membranous staining pattern in archival formalin-fixed, paraffin-embedded RBs. Results: A total of 60 RB cases and a RB cell line (Y79) were considered. The mean age at enucleation was 31.6 ± 31.5 months. The mean time from diagnosis to enucleation was 11.8 ± 11.2 months (range 1-44). Five (8%) cases were multifocal. HER2 overexpression was negative in all RB cases (49 cases scored 0 and 11 scored 1+) and in the Y79 cell line. Conclusions: Overall, we were not able to demonstrate the overexpression of HER2. Further studies should clarify and better elucidate the potential role of HER2-targeted therapies in RB.

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Expression of SIRT2 and SIRT6 in Retinoblastoma

Cited by 10 publications

References 37 publications

Tumour Expression of Histone Deacetylases in Uveal Melanoma

Tumour Expression of Histone Deacetylases in Uveal Melanoma

Sirtuin1 Expression and Correlation with Histopathological Features in Retinoblastoma

HER2 Overexpression in Retinoblastoma: A Potential Therapeutic Target

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