Abstract 2080: Differential transcription profile of epithelia in fimbria versus the ampulla of the fallopian tube

Abstract

Abstract Background: Recently described precursors of high-grade serous carcinoma (HGSC), the p53 signature, a latent precursor, and Serous Tubal Intraepithelial Carcinoma (STIC), a pre-malignant precursor, occur most frequently at the distal and fimbriated end of the fallopian tube (FTE). In 3 previous reports, we have demonstrated that the FTE of BRCA1 mutation carriers, at genetic risk of HGSC, have altered signaling pathways compared to controls. Ovarian production of ROS is released after the LH surge to induce ovulation. Reactive oxygen species (ROS) have been implicated in serous carcinogenesis. The objective of this study is to compare the transcriptome profiles of normal fimbria (high-risk epithelia prone to transformation) FTE and normal ampulla (low-risk epithelia) FTE which may lead to understanding the distal end of the fallopian tube as the preferential anatomic location of the fallopian to tube for cellular transformation. Method: Snap-frozen matched fimbria and ampulla tissues were controlled for age and ovarian cycle status. Cases included 12 luteal phase and 12 follicular phase women at no known risk for ovarian cancer. Laser capture microscopy was used to microdissect FTE cells, using 7-10 sections per case. Total RNA was isolated, RNA extracted and cDNA amplified. The expression profiles were generated using Affymetrix Human Genome HTA-2.0 Array. Results: Using gene level differential expression analysis with the Affymetrix Expression Console software, we performed unsupervised hierarchical clustering analysis with all 24 samples. We used a fold change of < -2 or > 2 and ANOVA p-value < 0.05 as a cut-off criteria for selecting genes. The cases clustered predominantly by ovarian cycle status rather than by their differences in anatomical origin or their matched pair. There were 427 genes differentially expressed amongst the 4 groups– Fim-Luteal, Fim-Follicular, FT-Luteal and FT-Follicular. Independent of ovarian cycle status, very few differences (35 genes– SALL1, ME1– higher in the ampulla; GSTA1, GSTA2, SERPINA3-higher in the fimbria– genes involved in metabolic pathways) were observed between the ampulla and fimbria FTE. Conclusions: The epithelia of the anatomically high-risk fallopian tube– the fimbria, show few differences in gene expression profiles compared to the lower risk portion– the ampulla. Expression differences predominantly are in response to the hormonal milieu, post-ovulation with an antioxidant program The increased anatomic risk of the fimbria is likely due to effects of the microenvironment, such as repeated exposure to follicular fluid at ovulation (higher ROS) and antioxidant genes and their interaction with DNA repair genes (like TP53), rather than intrinsic differences of the FTE in the two sites. Citation Format: Sophia H. George, Anca Milea, Noor Hera Salman, Patricia Ann Shaw. Differential transcription profile of epithelia in fimbria versus the ampulla of the fallopian tube. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2080. doi:10.1158/1538-7445.AM2015-2080