title: CCNE1 amplification and centrosome number abnormality in serous tubal intraepithelial carcinoma: further evidence supporting its role as a precursor of ovarian high-grade serous carcinoma.
abstract: Aberration in chromosomal structure characterizes almost all cancers and has profound biological significance in tumor development. It can be facilitated by various mechanisms including overexpression of cyclin E1 and centrosome amplification. As ovarian high-grade serous carcinoma has pronounced chromosomal instability, in this study we sought to determine whether increased copy number of CCNE1 which encodes cyclin E1 and centrosome amplification (>2 copies) occurs in its putative precursor, serous tubal intraepithelial carcinoma. We found CCNE1 copy number gain/amplification in 8 (22%) of 37 serous tubal intraepithelial carcinomas and 12 (28%) of 43 high-grade serous carcinomas. There was a correlation in CCNE1 copy number between serous tubal intraepithelial carcinoma and high-grade serous carcinoma in the same patients (P<0.001). There was no significant difference in the percentage of CCNE1 gain/amplification between serous tubal intraepithelial carcinoma and high-grade serous carcinoma (P=0.61). Centrosome amplification was recorded in only 5 (14%) of 37 serous tubal intraepithelial carcinomas, and in 10 (40%) of 25 high-grade serous carcinomas. The percentage of cells with centrosome amplification was higher in high-grade serous carcinoma than in serous tubal intraepithelial carcinoma (P<0.001). Induced expression of cyclin E1 increased the percentage of fallopian tube epithelial cells showing centrosome amplification. Our findings suggest that gain/amplification of CCNE1 copy number occurs early in tumor progression and precedes centrosome amplification. The more prevalent centrosome amplification in high-grade serous carcinoma than in serous tubal intraepithelial carcinoma supports the view that serous tubal intraepithelial carcinoma precedes the development of many high-grade serous carcinomas.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Kuhn
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Tian-Li
authors.initials: TL
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Penn Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Doberstein
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Asli
authors.initials: A
authors.lastname: Bahadirli-Talbott
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Pathology, Seirei Mikatahara Hospital, Hamamatsu, Japan.
authors.forename: Ayse
authors.initials: A
authors.lastname: Ayhan
authors.affiliation: Legacy Health Systems, Portland, OR, USA.
authors.forename: Ann Smith
authors.initials: AS
authors.lastname: Sehdev
authors.affiliation: Department of Obstetrics and Gynecology, Penn Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ronny
authors.identifier: 0000-0002-6912-6977
authors.initials: R
authors.lastname: Drapkin
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kurman
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
mesh_terms: D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D018385:Centrosome; D019927:Cyclin E / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D005185:Fallopian Tube Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D015513:Oncogene Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins