[1146] MicroRNA Signatures in Early and Later Stage of High Grade Serous Carcinoma in Fallopian Tube.

Jian-Jun Wei, Zhaojian Liu, Jingjing Wu. Northwestern University, Chicago, IL

Background: High grade papillary serous carcinoma (HG-PSC) of the ovaries/fallopian tubes is one of the most lethal gynecological malignancies. Recent studies have raised a compelling hypothesis that fallopian tube (FT) secretory epithelial cells may harbor a cell of origin for most HG-PSC. About 80% of HG-PSC precursor lesions, also known as serous tubal intraepithelial carcinoma (STIC), are found in the distal (fimbriated) ends of the fallopian tubes. Beyond p53 mutations, the molecular changes of STIC are largely unknown.
Design: To explore the molecular difference between normal FT, STIC and invasive HG-PSC, we conducted a global microRNA expression analysis. In our well characterized cases presenting with normal FT, STIC and HG-PSC, we selected five cases for miRNA profiling analysis and 12 cases for validation by RT-PCR and microRNA in situ hybridization (MISH). In each case, areas of FT, STIC and PSC were microdissected from 10 um sections in formalin fixed paraffin embedded tissue (FFPE). MTG platform was used for global microRNA profiling analysis, including 700 well characterized microRNAs. ANOVA significance analysis was performed to identify microRNAs above 2 fold changes.
Results: MicroRNA expression profiles were successfully accomplished in FFPE tissues. All cases examined had reasonable clean microRNA data and had good agreement within each component. The net changes of microRNA expression and distinct microRNA signatures among different components were established. Table 1 summarized the numbers of microRNAs differentially expressed (>2 folds) between FT and STIC, STIC and PSC, FT and PSC. Top dysregulated microRNAs, including miR182, miR200c, miR34s, miR210 and miR93, were confirmed by RT-PCR and some were further validated by MISH.

Differential miRNA expression in FT, STIC and PSC
downregulated miRNA141617
upregulated miRNA33264
fold ranges2-92-502-6
FT: fallopian tube; STIC: serous tubal intraepithelial carcinoma; PSC: invasive high grade serous carcinoma

Conclusions: STIC is early stage of HG-PSC and it has distinct microRNA expression and it can be discriminated by its unique microRNA signature from FT and HG-PSC. Top dysregulated microRNAs in HG-PSC have a high agreement with published data. We were able to identify a subset of oncogenic microRNAs differentially expressed between FT, STIC and PSC. This novel finding will provide molecular tools for the further analysis of tumorigenesis of STIC and will benefit in searching for new biomarkers (microRNA target genes) for STIC.
Category: Gynecologic & Obstetrics

Wednesday, March 2, 2011 9:30 AM

Poster Session V # 135, Wednesday Morning


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