Shortened telomeres in serous tubal intraepithelial carcinoma: An early event in ovarian high-grade serous carcinogenesis

Elisabetta Kuhn, Alan Meeker, Tian Li Wang, Ann Smith Sehdev, Robert J. Kurman, Ie Ming Shih

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Short telomeres are one of the main genetic manifestations in human cancer, as they have been shown to play an important role in inducing chromosomal instability and in contributing to tumor progression. The purpose of this study was to determine if changes in telomere length occur in serous tubal intraepithelial carcinoma (STIC), the putative precursor of "ovarian" high-grade serous carcinoma (HGSC). Twenty-two STICs from 15 patients with concurrent but discrete HGSCs were analyzed for telomere length on formalin-fixed, paraffin-embedded sections by conducting p53 immunofluorescence to assist in identifying STICs and telomere-specific FISH. Telomere length (short, long, or no change) in STICs was compared with HGSCs using normal fallopian tube epithelium and stromal cells as controls. We found that STICs had the shortest telomeres, as 18 (82%) of 22 STICs had short telomeres, whereas only 2 (9%) showed no change and 2 (9%) had long telomeres compared with the normal-looking tubal epithelium. In contrast, among 12 paired HGSCs and STICs, 6 HGSCs showed an increase in telomere length, one showed a decrease in length and 5 did not show any change when compared with their matched STICs, although, such as STICs, the majority of HGSCs had shorter telomeres than the associated normal tubal epithelial cells. These differences in telomere length between normal tubal epithelial cells and STICs, and between STICs and HGSCs were statisticaly significant (P<0.05). In conclusion, the finding of short telomeres, which have been shown to be one of the earliest molecular changes in carcinogenesis, in a vast majority of STICs provides further support to the proposal that STICs are precursors of HGSC and opens new areas of research in elucidating the early events of ovarian high-grade serous carcinogenesis.

Original languageEnglish (US)
Pages (from-to)829-836
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume34
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • High-grade serous carcinoma
  • Ovarian cancer
  • Serous tubal intraepithelial carcinoma
  • Telomere

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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