Expression pattern of class I histone deacetylases in vulvar intraepithelial neoplasia and vulvar cancer: a tissue microarray study

外阴上皮内瘤变和外阴癌中 I 类组蛋白去乙酰化酶的表达模式:组织微阵列研究

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作者:Nicolas Samartzis, Patrick Imesch, Konstantin J Dedes, Eleftherios P Samartzis, André Fedier, Daniel Fink, Rosmarie Caduff, Mathias K Fehr

Background

Epigenetic regulation is an important mechanism leading to cancer initiation and promotion. Histone acetylation by histone deacetylases (HDACs) represents an important part of it. The development of HDAC inhibitors has identified the utility of HDACs as a therapeutic target. Little is known about the epigenetic regulation of vulvar intraepithelial neoplasia (VIN) and vulvar squamous cell cancer (VSCC). In this study, the expression of class I HDACs (HDAC 1, 2 and 3) was compared in a series of VIN and VSCC tissues.

Conclusions

These results suggest that epigenetic regulation plays a considerable role in the transformation of VIN to invasive vulvar neoplasia.

Methods

A tissue micro array (TMA) with specimens from 106 patients with high-grade VIN and 59 patients with vulvar cancer was constructed. The expression of HDACs 1, 2 and 3 were analyzed with immunohistochemistry (IHC). The nuclear expression pattern was evaluated in terms of intensity and percentage of stained nuclei and was compared between vulvar preinvasive lesions and vulvar cancer.

Results

HDAC 2 expression was significantly higher in VIN than in VSCC (p < 0.001, Fisher's test). Also, 88.7% (n = 94/106) of VIN samples and only 54.5% (n = 31/57) of VSCC samples were scored at the maximum level. Conversely, HDAC 3 expression was significantly higher in VSCC (93%, 53/57) compared to VIN (73.6%, 78/106, p = 0.003), whereas only a small difference in the expression of HDAC 1 was found between these two entities of vulvar neoplasia. Conclusions: These results suggest that epigenetic regulation plays a considerable role in the transformation of VIN to invasive vulvar neoplasia.

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