title: Global histone acetylation levels: prognostic relevance in patients with renal cell carcinoma.
abstract: Epigenetic alterations play an important role in carcinogenesis. Recent studies have suggested that global histone modifications are predictors of cancer recurrence in various tumor entities. Global histone acetylation levels (histone H3 lysine 9 acetylation [H3K9Ac], histone H3 lysine 18 acetylation [H3K18Ac], total histone H3 acetylation [H3Ac] and total histone H4 acetylation [H4Ac]) were determined in patients with renal cell carcinoma (RCC) using immunohistochemistry in a tissue micro array with 193 RCC and 10 oncocytoma specimens. The histone acetylation pattern was not different among the diverse histological subtypes of RCC or oncocytoma samples. The H3Ac levels were inversely correlated with pT-stage (P = 0.005), distant metastasis (P = 0.036), Fuhrman grading (P = 0.001) and RCC progression (P = 0.029, hazard ratio 0.87). H4Ac deacetylation was correlated with pT-stage (P = 0.011) and grading (P = 0.029). H3K18Ac levels were an independent predictor of cancer-progression following surgery for localized RCC in the univariate (P = 0.001, hazard ratio 0.78) and multivariate (P = 0.005, hazard ratio 0.82) analysis. In conclusion, our study supports the concept of global histone modification levels as a universal cancer prognosis marker, and provides evidence for the use of histone deacetylases inhibitors as future drugs in the therapy of RCC.
authors.affiliation: Department of Urology, University Hospital Bonn, Bonn, Germany.
authors.forename: Davit
authors.initials: D
authors.lastname: Mosashvilli
authors.forename: Philip
authors.initials: P
authors.lastname: Kahl
authors.forename: Claudia
authors.initials: C
authors.lastname: Mertens
authors.forename: Stefanie
authors.initials: S
authors.lastname: Holzapfel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rogenhofer
authors.forename: Stefan
authors.initials: S
authors.lastname: Hauser
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.forename: Alexander
authors.initials: A
authors.lastname: Von Ruecker
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D044127:Epigenesis, Genetic; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D006657:Histones
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