Differential Expression of MicroRNAs in Craniopharyngioma

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 164-196-Pituitary
Basic/Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-175
Jill H. Samis*1, Elio F. Vanin2, Fabricio F. Costa2, Reema L. Habiby3, Simone T. Sredni2, Stewart Goldman3, Tadanori Tomita3, Donald Zimmerman3 and Marcelo B. Soares2
1Rush University Medical Center, Chicago, IL, 2Ann and Robert H. Lurie Children's Hospital of Chicago Research Center, Chicago, IL, 3Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
Background:  Craniopharyngiomas are benign tumors of the sellar or parasellar regions that invade surrounding brain structures often producing hypothalamic and pituitary dysfunction, visual impairment, and obstructive hydrocephalus.  Current therapies include surgery, with or without radiation therapy, leading to long-term pituitary hormone deficiencies and cognitive deficits.  There is little information on the role of microRNAs (miRNAs) in development of craniopharyngiomas, in predicting tumors with a propensity to recur, and on their use in identifying novel therapies.

Hypothesis:  Craniopharyngiomas are a developmental disease in which aberrations in the normal epigenetic regulatory events may lead to the development of craniopharyngioma instead of the normal pituitary gland.  In addition, craniopharyngiomas with a propensity to recur or progress have different miRNA expression profiles from those that are less aggressive. 

Methods:  Primary and recurrent formalin-fixed, paraffin-embedded (FFPE) craniopharyngioma samples from nineteen patients, ten age-matched pituitary samples from autopsy, and ten infant pituitary samples from autopsy were obtained from the Department of Pathology at Ann and Robert H. Lurie Children’s Hospital of Chicago.  Total RNA was extracted and miRNA expression evaluated using the Applied Biosystems TaqMan® Real-Time PCR with over 700 miRNAs represented.  RealTime StatMiner® (Integromics®) was used to identify the differentially expressed miRNAs between tumors and controls as well as tumors that recurred compared to those that did not recur.

Results:  Approximately thirty differentially expressed miRNAs were identified in craniopharyngiomas when compared to infant pituitary samples and when compared to age-matched controls (p ≤ 1x10-8).  Many of the miRNAs identified were down-regulated in both of the comparisons, while other differentially expressed miRNAs were unique when compared to either the age-matched controls or infant pituitary samples.  Additionally, miR-199a-5p was identified to be down-regulated in craniopharyngiomas that recurred as opposed to those which did not have a recurrence (p=0.05).

Conclusions:  There are multiple miRNAs that are differentially expressed in craniopharyngiomas as compared to both normal and infant pituitary tissue.  These miRNAs may play a role in the development and biological behavior of craniopharyngiomas.  Additionally, miR-199a-5p may play a role in craniopharyngiomas that recur and may function as a prognostic marker or potential therapeutic target.

Nothing to Disclose: JHS, EFV, FFC, RLH, STS, SG, TT, DZ, MBS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Matthew Larson Foundation