Immunohistochemical Expression of Dicer in Soft tissue Sarcomas: Association with Prognostic Significance
DJ Papachristou, A Palekar, J McDavit, D Bartlett, MA Goodman, UNM Rao. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: MicroRNAs (miR) are small 18-23 nucleotide-long, non-coding RNAs that regulate vital cellular processes. The generation of mature miR from pre-miR, is mediated by a RNase III-related endonuclease, called Dicer. Dicer altered expression is associated with poor survival in several carcinomas. Nonetheless, the expression and function of this enzyme has never been studied in human mesenchymal neoplasms. Herein, we investigate the expression of Dicer in a panel of soft tissue tumors (STT) and tested its association with clinicopathologic parameters including survival.
Design: Our study was approved by the University of Pittsburgh Institutional Review Board (IRB: 612060). Totally 142 STT (40 benign, 102 malignant [73 high-, 29 low-grade]) as well as reactive and normal tissues were used for the construction of two TMAs. Follow-up data: mean follow-up period=37.6 months, median=33.0, STD=26.2, range=1-115 months. Standard immunohistochemistry was applied (anti-Dicer antibody, Clonegene, Hartford, CT, USA). Immunoreactivity was graded on a scale of 1-3 according to the staining intensity.
Results: 1) Dicer cytoplasmic immunoreactivity was observed in 125/142 of the examined neoplasms, but not in normal mesenchymal tissues. 2) Dicer expression levels were significantly higher in malignant compared to benign and in high- compared to low-grade tumors (Kendall's t, p<0.0001, for all). 3) Augmented Dicer levels were significantly and positively correlated with metastatic potential and patients' death (Kendall's t, p<0.005, for all). 4) Increased Dicer immunoreactivity, elevated tumor grade and size >5cm correlated with increased metastatic potential (p<0.005) and worse overall survival (Kaplan-Meier, p=0.0005, 0.004 and 0.017, respectively). 5) Dicer expression and tumor size, were independent predictors of poor outcome (COX analysis, log-rank p=0.003 and 0.005, respectively).
Conclusions: 1) Dicer is widely expressed in human STT. 2) Abnormal Dicer expression in soft tissue sarcomas (STS) suggests that miR machinery might be implicated in their pathobiology. 3) Dicer can be used for the prediction of STS with increased metastatic potential and poorer survival. 4) Increased Dicer expression might help to predict the efficiency of future RNA interference-based anti-STS therapeutic strategies.
Category: Bone & Soft Tissue
Monday, March 9, 2009 1:00 PM
Poster Session II # 16, Monday Afternoon