4.6 Article

Immunohistochemical evaluation of stress-responsive protein sestrin2 and its correlation with p53 mutational status in eyelid sebaceous gland carcinoma

期刊

BRITISH JOURNAL OF OPHTHALMOLOGY
卷 102, 期 6, 页码 848-854

出版社

BMJ PUBLISHING GROUP
DOI: 10.1136/bjophthalmol-2017-311283

关键词

pathology; eye lids; neoplasia

资金

  1. Delhi University Innovation project [SVC-302]

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Background p53 is a stress-activated tumour suppressor gene, and its mutation has been associated with solid tumours including non-melanoma skin cancers. Sestrin2 expression is associated with DNA damage and oxidative stress and has been described as a downstream target of p53 network. However, its role in sebaceous gland carcinoma (SGC) remains unexplored. Objectives To determine the role of p53 and its downstream target gene sestrin2 expression and p53 gene mutation status in SGC. Methods Twenty cases of eyelid SGC tumour and circulating cell-free DNA (ccfDNA) were subjected to mutational analysis of p53 gene. p53 and sesrin2 expression was evaluated by immunohistochemistry. Results were correlated with the clinicopathological features of eyelid SGC. Results p53 gene mutations was detected in 25% of the SGC cases. A C>Ttransition was identified in exon 6 in a single patient in both tumour and ccfDNA. A G>Ttransversion leading to amino acid change D259Y was seen in four patients. A splice site mutation affected a single case in exon 6. p53 expression was observed in 55% SGC. Loss of sestrin2 in 55% SGC cases correlated with poor tumour differentiation (P=0.0001), upper eyelid involvement (P=0.004), p53 mutation (P=0.039) and with mutant p53 expression (P=0.0001). Conclusion Sestrin2 expression was found to be significantly reduced in p53 mutated SGC cases and in cases with strong p53 nuclear immunopositivity, suggesting that loss of sestrin2 may be of biological significance in the development of SGC and as a key downstream component of p53 tumour suppression network in eyelid SGC.

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