miR-146a Expression in Cervical Squamous Cell Carcinoma
Ling Xue, Krishan Kalra, Mahul Amin, Shikha Bose, Raju Pillai. BioGenex Laboratories, Fremont, CA; Cedars-Sinai Medical Center, Los Angeles, CA
Background: MicroRNA (miRNA) are short single stranded RNA molecules that act as post-transcriptional regulators by binding to complementary sequences on target messenger RNA transcripts. miR-146a, initially characterized as playing an important role in innate immune response to microbial infection, has been implicated in recent studies in control of cell growth, differentiation and survival. Lower miR-146a expression has been associated with more extensive lymph node metastasis and venous invasion in gastric and breast carcinoma. However, the expression of miR-146a in cervical squamous cell carcinoma (SCC-Cx) and its role in prognosis is not fully established. It has been reported that miR-218 levels in patients with high-risk CIN were lower than in those with low-risk CIN. In this study, we have examined the expression of miR-146a and miR-218 in SCC-Cx.
Design: Tissue microarrays were constructed from 60 cases of SCC-Cx and 10 normal Cx biopsies. FAM-labeled scramble probe (BioGenex, PR032), miR-146a (BioGenex, HM146A), mutant miR-146a (BioGenex, HM146AM), miR-218 (BioGenex, HM218) and One-step ISH Detection Kit (BioGenex, DF400) were used in this study. Briefly, following dewaxing and rehydration, FFPE tissue slides were heated in Nucleic Acid Retrieval Solution I (NAR-I, Biogenex) for 10 min at 92C. After incubation with 40 nM of microRNA probe for 60 min at 50 C, the signal was amplified with anti-fluorescein antibody and poly-HRP detection system.
Results: The expression of miR-146a was up-regulated in 40/60 (67%) of SSC-Cx cases (see figure) and 20/60 (33%) SCC-Cx cases exhibited basal level of expression. Most cases with increased miR-146 expression had moderately to poorly differentiated morphology. miR-218 was up-regulated in 14/60 (23.3%), basal levels were seen in 34/60 (56.7%), and was down-regulated in 12/60 (20%) of cervical cancer samples.
Conclusions: SCC-Cx cases showed upregulation of miR-146a in the majority of cases and showed a trend towards increased expression in moderately to poorly differentiated SCC-Cx. miR-218 expression was decreased in most SSC-Cx cases. Larger studies to examine the prognostic implications of these two markers are warranted.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 231, Tuesday Afternoon