Shorter Telomere Length in Most Serous Tubal Intraepithelial Carcinomas
E Kuhn, A Meeker, A Smith Sehdev, RJ Kurman, IM Shih. Johns Hopkins Medical Institutions, Baltimore, MD
Background: Telomere length shortening has been well known as one of the main genetic manifestations in human cancer. The shortened telomere plays an important role in inducing genomic instability and propelling tumor progression. The purpose of this study is to determine if changes in telomere length occurs in serous tubal intraepithelial carcinoma (STIC), a putative precursor of “ovarian” high-grade serous carcinomas.
Design: A total of 23 STICs from 15 patients who had concurrent pelvic high-grade serous carcinoma were analyzed for telomere length. All STICs were discrete from the carcinomas. Paraffin-embedded tissue sections were prepared for telomere FISH. p53 immunofluorescence was also co-applied to confirm STICs, thus facilitating the scoring of telomere length. The concurrent high-grade serous carcinomas were also analyzed from the same patients. The telomere length in STICs and carcinoma was compared to normal fallopian tube epithelium and scored as abnormally short, no change or abnormally long using a quantitative imaging analysis system.
Results: We found that 16 (84.2%) of 19 STICs harbored significantly shorter telomeres, while only 1 (5.3%) showed no change and 2 (10.5%) had longer telomeres. In high-grade serous carcinomas, shortened telomeres occurred in 8 (66.7%) of 12 carcinomas while longer telomeres were found in 4 (33.3%) cases. The pattern of telomere length change was the same in both STICs and carcinoma from the same patients in 83.3% of cases. Among all 9 patients in which their STICs had shorter telomere, 8 of them also demonstrated shorter telomere in their corresponding carcinomas. In multifocal STICs from the same patients, all STICs showed the same pattern of telomere length change.
Conclusions: The above findings lend further support to the proposal that STIC is a precursor of high-grade serous carcinoma and suggests that telomere alteration is one of the earliest molecular changes in the development of high-grade serous carcinomas. This new finding is consistent with previous observations of increased DNA damage (as evidenced by γH2AX) and aneuploidy in STICs and has important implications for the further studies on pathogenesis of pelvic serous carcinoma.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 148, Tuesday Afternoon