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


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.
Department of Gynecology, University Hospital Zurich, Frauenklinikstrasse 10, 8091 Zurich, Switzerland.
Nicolas
N
Samartzis
Patrick
P
Imesch
Konstantin J
KJ
Dedes
Eleftherios P
EP
Samartzis
André
A
Fedier
Daniel
D
Fink
Rosmarie
R
Caduff
Mathias K
MK
Fehr
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000201:enzymology*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D005260:Female; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D046888:Tissue Array Analysis / Q000379:methods; D014846:Vulvar Neoplasms / Q000201:enzymology* / Q000473:pathology; D055815:Young Adult
D009363:Neoplasm Proteins; D056284:Histone Deacetylase 1