title: Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer.
abstract: Chromatin remodeling alters gene expression in carcinoma tissue. Although cervical cancer is the fourth most common cancer in women worldwide, a systematic study about the prognostic value of specific changes in the chromatin structure, such as histone acetylation or histone methylation, is missing. In this study, the expression of histone H3 acetyl K9, which is known to denote active regions at enhancers and promoters, and histone H3 tri methyl K4, which preferentially identifies active gene promoters, were examined as both show high metastatic potential. A panel of patients with cervical cancer was selected and the importance of the histone modifications concerning survival-time (overall survival and relapse-free survival) was analyzed in 250 cases. Histone H3 acetyl K9 staining was correlated with low grading, low FIGO (TNM classification and the International Federation of Gynecology and Obstetrics) status, negative N-status and low T-status in cervical cancer, showing a higher expression in adenocarcinoma than in squamous cell carcinoma. Cytoplasmic expression of histone H3 tri methyl K4 in a cervical cancer specimen was correlated with advanced T-status and poor prognosis. While cytoplasmic H3K4me3 expression seemed to be a marker of relapse-free survival, nuclear expression showed a correlation to poor prognosis in overall survival. Within this study, we analyzed the chemical modification of two histone proteins that are connected to active gene expression. Histone H3 acetyl K9 was found to be an independent marker of overall survival. Histone H3 tri methyl K4 was correlated with poor prognosis and it was found to be an independent marker of relapse-free survival. Therefore, we could show that chromatin remodeling plays an important role in cervical cancer biology.
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, 80337 Munich, Germany. sannebeyer@yahoo.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Beyer
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, 80337 Munich, Germany. Junyan.Zhu@med.uni-muenchen.de.
authors.forename: Junyan
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Ludwig-Maximilians-University of Munich, 80337 Munich, Germany. doris.mayr@med.uni-muenchen.de.
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, 80337 Munich, Germany. christina.kuhn@med.uni-muenchen.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Kuhn
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, 80337 Munich, Germany. Sandra.schulze@med.uni-muenchen.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schulze
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, 80337 Munich, Germany. simone.hofmann@med.uni-muenchen.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Hofmann
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, 80337 Munich, Germany. Christian.dannecker@med.uni-muenchen.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Dannecker
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, 80337 Munich, Germany. udo.jeschke@med.uni-muenchen.de.
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, 80337 Munich, Germany. bernd.kost@med.uni-muenchen.de.
authors.forename: Bernd P
authors.initials: BP
authors.lastname: Kost
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008875:Middle Aged; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones
keywords: cervical cancer; chromatin modification; epigenetics; histone H3 acetyl K9; histone H3 tri methyl K4; histone proteins; prognosis