Elsevier

Human Pathology

Volume 33, Issue 6, June 2002, Pages 632-641
Human Pathology

Original Contributions
Genetic alterations in epithelial ovarian tumors analyzed by comparative genomic hybridization*

https://doi.org/10.1053/hupa.2002.124913Get rights and content

Abstract

The genetic changes involved in the pathogenesis of ovarian carcinoma are not completely understood. To investigate this matter, we studied paraffin-embedded, microdissected tissue of 47 ovarian epithelial tumors (9 adenomas, 11 tumors of low malignant potential [LMP], 14 serous carcinomas, and 13 nonserous carcinomas) using comparative genomic hybridization (CGH). (The primary data used in this study are available at our CGH online tumor database at http://amba.charite.de/cgh.) Chromosomal imbalances were found in 1 serous adenoma and in 7 LMP tumors. In the latter the alterations appeared randomly and showed no overlap with alterations found in invasive carcinomas. Although the mean aberration number of low-grade serous carcinomas was comparable to LMP tumors, the imbalances of the former occurred with high incidence (>50%) and were found at different localizations. High-grade serous carcinomas had more than twice as much chromosomal imbalances as low-grade serous carcinomas and also had pronounced alterations. In serous carcinomas, gains were found on 3q, 6p, 7, 8q, and 20, and losses were found on 4q, 6q, 12q, 13q, and 16q. Comparing serous and nonserous carcinomas, the mean aberration number was comparable, but the number of high incidence changes was lower, and the most frequent imbalances were losses on 13q and gains on 20p. Overlapping alterations occurring in serous and nonserous carcinomas were gains on 3q and 6p, as well as losses on 4q. Chromosomal imbalances associated with poor prognosis of ovarian carcinomas were gains on 6p, 7q, and 13q and losses on 15q, 17p, 18q, and 21q. Our data indicate that serous LMP tumors and invasive carcinomas have different genetic aberrations, indicating that invasive carcinomas do not arise from preexisting serous LMP tumors. On the other hand, there are common genetic abnormalities in serous and nonserous carcinomas, suggesting that they have very early lesions in common but take different paths of further development. HUM PATHOL 33:632-641. Copyright 2002, Elsevier Science (USA). All rights reserved.

Section snippets

Patient characteristics

The study group comprised 45 patients presenting with benign or malignant tumors of the ovary (Table 1).We studied 9 patients with benign lesions; 5 patients had serous cystadenomas (mean age, 60 years; mean size, 52 mm; 3 left, 2 right), 1 28-year-old patient had an endometriotic cyst, and 3 patients had benign Brenner tumors (mean age, 43 years; mean size, 35 mm; 2 right, 1 left).

Eleven LMP tumors from 10 patients of mean age 51 years were investigated: 5 of these tumors were serous, 3 were

Results

Chromosomal imbalances were found in only 1 serous adenoma, which had losses on 1p36, 19, and 22 (Table 2).Aberrations were found in 7 of 11 LMP tumors (5 serous, 1 mucinous, and 1 endometrioid). On average, there were 4.0 gains and 3.8 losses. The losses were found most consistently on 1p36, 16p, 19, and 22, the former on 3p26 (Table 2). In the group of serous LMP tumors, we found 3.6 gains and 4.7 losses. The bilateral LMP tumor studied had very similar chromosomal imbalances on both sites

Discussion

Although various genetic studies on ovarian cancer have been performed, no consistent pattern of genetic alterations has been defined until now. The reason for this lack of consistency is that most of these studies use heterogeneous tumor material, mixing not only the various histologic types of ovarian cancer, but also germ cell tumors and epithelial tumors.9, 10, 11, 12 Moreover, the different methods used to analyze genetic alterations reduce the comparability of the studies. This has been

References (54)

  • K Roth et al.

    Image analysis for comparative genomic hybridization by a Windows-based karyotyping program

    Anal Quant Cytol Histol

    (1997)
  • DH Moore et al.

    A t-statistic for objective interpretation of comparative genomic hybridization (CGH) profiles

    Cytometry

    (1997)
  • J Zheng et al.

    Distinction of low-grade from high-grade ovarian cacinomas on the basis of losses of heterozygosity on chromosomes 3, 6 and 11 and HER-2/neu gene amplification

    Cancer Res

    (1991)
  • B Vandamme et al.

    Deletion of chromosome 11p13-11p15.5 sequences in invasive human ovarian cancer is a subclonal progression factor

    Cancer Res

    (1992)
  • H Iwabuchi et al.

    Genetic analysis of benign, low-grade, and high-grade ovarian tumors

    Cancer Res

    (1995)
  • R Taetle et al.

    Chromosome abnormalities in ovarian adenocarcinoma: I. Nonrandom chromosome abnormalities from 244 cases

    Genes Chromosomes Cancer

    (1999)
  • N Arnold et al.

    Overrepresentation of 3q and 8q material are recurrent findings in advanced human ovarian cancer

    Genes Chromosomes Cancer

    (1996)
  • J Tapper et al.

    Evidence for divergence of DNA copy number changes in serous, mucinous and endometrioid ovarian carcinomas

    Br J Cancer

    (1997)
  • G Sonoda et al.

    Comparative genomic hybridization detects frequent overexpression of chromosomal material from 3q26, 8q24, and 20q13 in human ovarian carcinomas

    Genes Chromosomes Cancer

    (1997)
  • NG Wolf et al.

    Analysis of ovarian borderline tumors using comparative genomic hybridization and fluorescence in situ hybridization

    Genes Chromosomes Cancer

    (1999)
  • S Deger et al.

    Karyotypic analysis of 32 epithelial ovarian tumors

    Cancer Genet Cytogenet

    (1997)
  • M Kiechle et al.

    Comparative genomic hybridization detects genetic imbalances in primary ovarian carcinomas as correlated with grade of differentiation

    Cancer

    (2001)
  • S Hauptmann et al.

    Serous tumors of low malignant potential (SLMP) of the ovary—Molecular pathology (part 2 of 2)

    Virchows Arch

    (2001)
  • RT Burks et al.

    Micropapillary serous carcinoma of the ovary. A distinctive low-grade carcinoma related to serous borderline tumors

    Am J Surg Pathol

    (1996)
  • T Pejovic et al.

    Chromosomal aberrations in 35 primary ovarian carcinomas

    Genes Chromosomes Cancer

    (1992)
  • MF Evans et al.

    Numerical abnormalities of chromosomes 1, 11, 17, and X are associated with stromal invasion in serous and mucinous epithelial ovarian tumors

    J Pathol

    (1999)
  • MJ Bello et al.

    Chromosome aberrations in metastatic ovarian cancer: Relationship with abnormalities in primary tumors

    Int J Cancer

    (1990)
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    *

    Address correspondence and reprint requests to Steffen Hauptmann, MD, Institute of Pathology, Charité Hospital Berlin, Schumannstr. 20/21, D-10117 Berlin, Germany.

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