Analysis of Telomere Lengths in p53 Signatures and Incidental Serous Tubal Intraepithelial Carcinomas Without Concurrent Ovarian Cancer

Shiho Asaka, Christine Davis, Shiou Fu Lin, Tian-Li Wang, Christopher M. Heaphy, Ie Ming Shih

Research output: Contribution to journalArticle

Abstract

Telomere alterations represent one of the major molecular changes in the development of human cancer. We have previously reported that telomere lengths in most serous tubal intraepithelial carcinomas (STIC) are shorter than they are in ovarian high-grade serous carcinomas (HGSC) or in normal-Appearing fallopian tube epithelium from the same patients. However, it remains critical to determine if similar telomere alterations occur in TP53-mutated but histologically unremarkable "p53 signature" lesions, as well as incidental STICs without concurrent HGSC. In this study, we quantitatively measured telomere lengths by performing telomere-specific fluorescence in situ hybridization in conjunction with p53 immunolabeling in 15 p53 signatures and 30 incidental STICs without concurrent HGSC. We compared these new results with our previous data in paired STICs and concurrent HGSCs. We found that most p53 signatures (80%) and incidental STICs without HGSC (77%) exhibited significant telomere shortening compared with adjacent normal-Appearing fallopian tube epithelium (P<0.01). Interestingly, however, p53 signatures and incidental STICs without HGSC displayed longer telomeres and less cell-To-cell telomere length heterogeneity than STICs associated with HGSC (P<0.001). These findings indicate that telomere shortening occurs in p53 signatures, the earliest precancer lesion. Moreover, incidental STICs without concurrent HGSC are indeed similar to p53 signatures as they have less telomere shortening and less cell-To-cell telomere length heterogeneity than STICs associated with HGSC.

Original languageEnglish (US)
Pages (from-to)1083-1091
Number of pages9
JournalAmerican Journal of Surgical Pathology
Volume43
Issue number8
DOIs
StatePublished - Aug 1 2019

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Carcinoma in Situ
Telomere
Ovarian Neoplasms
Carcinoma
Telomere Shortening
Fallopian Tubes
Epithelium
Human Development
Fluorescence In Situ Hybridization

Keywords

  • fallopian tube
  • ovarian cancer precursor
  • p53 signature
  • serous tubal intraepithelial carcinoma
  • telomere

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Analysis of Telomere Lengths in p53 Signatures and Incidental Serous Tubal Intraepithelial Carcinomas Without Concurrent Ovarian Cancer. / Asaka, Shiho; Davis, Christine; Lin, Shiou Fu; Wang, Tian-Li; Heaphy, Christopher M.; Shih, Ie Ming.

In: American Journal of Surgical Pathology, Vol. 43, No. 8, 01.08.2019, p. 1083-1091.

Research output: Contribution to journalArticle

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