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

Asaka, Shiho MD, PhD*; Davis, Christine BS; Lin, Shiou-Fu MD; Wang, Tian-Li PhD*,†,‡; Heaphy, Christopher M. PhD*,†; Shih, Ie-Ming MD, PhD*,†,‡

The American Journal of Surgical Pathology: August 2019 - Volume 43 - Issue 8 - p 1083–1091
doi: 10.1097/PAS.0000000000001283
Original Articles
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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.

Departments of *Oncology

Pathology

Gynecology and Obstetrics, The Sidney Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD

Conflicts of interest and Source of Funding: This work was supported by the Department of Defense CDMRP W81XWH-11-2-0230; NIH/NCI P50CA228991 and UO1CA200469; the Honorable Tina Brozman Foundation, Ovarian Cancer Research Alliance, Teal award, Roseman Foundation, Gray foundation and the Richard W. TeLinde Endowment from the Johns Hopkins University. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Christopher M. Heaphy, PhD, Departments of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21231 (e-mail: cheaphy@jhmi.edu).

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