title: Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma.
abstract: Epigenetic alterations play an important role in carcinogenesis. Recent studies suggested that global histone modifications are predictors of cancer recurrence in various tumor entities. Our study was performed to evaluate histone H3 lysine 4 mono-methyl (H3K4me1), -di-methyl (H3K4me2) and -trimethyl (H3K4me3) patterns in renal cell carcinoma (RCC) using a tissue microarray with 193 RCC (including 142 clear cell, 31 papillary, 10 chromophobe and 10 sarcomatoid RCC) and 10 oncocytoma specimens: H3K4me3 staining was more intense in papillary RCC, whereas H3K4me1 and H3K4me2 were similar in the diverse RCC subtypes. H3K4me2 and H3K4me3 levels were increased in oncocytoma. H3K4me1-3 levels were inversely correlated with Fuhrman grading, pT stage, lymph node involvement and distant metastasis. Progression-free survival and cancer-specific survival were shorter in patients with low levels of H3K4me1-3 in the univariate analysis, but we did not observe a significant correlation of a single modification in a multivariate model, which also included the established prognostic parameters TNM-stage and Fuhrman grade. In comparison, the H3K4me score, which combined staining levels of the H3K4 modifications, was an independent predictor of RCC progression-free survival. Our study on H3K4 methylation supports the concept of global histone modifications as potential cancer prognosis markers.
authors.affiliation: Klinik und Poliklinik für Urologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.forename: Philip
authors.initials: P
authors.lastname: Kahl
authors.forename: Claudia
authors.initials: C
authors.lastname: Mertens
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rogenhofer
authors.forename: Stefan
authors.initials: S
authors.lastname: Hauser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hartmann
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Alexander
authors.initials: A
authors.lastname: von Ruecker
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D011379:Prognosis
chemical_list: D006657:Histones; D008239:Lysine