MicroRNAs Differentiate Low and High-Risk Endometrial Carcinomas
JF Snowdon, X Zhang, TJ Childs, VA Tron, H Feilotter. Queen's University, Kingston, ON, Canada
Background: Endometrial carcinoma is the most common gynecologic malignancy in industrialized nations and is clinically classified as low-, intermediate-, or high-risk based on clinico-pathologic staging criteria. Treatment decisions are based on this risk assessment and accurate prediction of patients who are likely to recur can reduce unnecessary adjuvant treatment. Currently, there are few molecular biomarkers that assist in the differentiation of these categories. MicroRNAs (miRNAs, miRs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. MicroRNA expression can be dysregulated in cancer and this may impact tumorigenesis through altered regulation of cell proliferation, apoptosis, invasion/metastasis, and angiogenesis. Additionally, miRNAs have been shown to have prognostic and diagnostic value in certain types of cancer.
Design: We compared the expression profiles of 723 human miRNAs from low (n=5), intermediate (n=17), and high (n=4) risk formalin-fixed paraffin-embedded (FFPE) endometrial carcinomas using Agilent Human miRNA arrays. Differentially expressed miRNAs were identified and potential mRNA targets were identified using miRBase.
Results: We identified 5 miRNAs whose expression pattern was significantly different between the low and high-risk tumors (p<0.05). Four of the microRNAs (miR-106a, miR-130a, miR-18a, and miR-885-5p) were down-regulated, while miR-424 was up-regulated in the low-risk tumors compared to the high-risk tumors. Four of these dysregulated miRNAs (miR-106a, miR130a, miR-18a, and miR424) have predicted or validated targets related to tumorigenesis or poor prognosis in other tumor types.
Conclusions: These preliminary results show that miRNAs can be used to stratify endometrial carcinomas into low- and high-risk groups. This information can be used to identify important steps in tumour progression that could be exploited for cancer treatment. Additionally, these results show that miRNAs could be useful for prognostication or pre-operative risk assessment in this tumor type.
Category: Gynecologic & Obstetrics
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 164, Monday Morning