Specific MicroRNAs Differentiate between Adrenocortical Adenomas and Carcinomas
M Feinmesser, C Benbassat, G Toren-Haritan, N Barabash, T Drozd, Y Spector. Rabin Medical Center, Beilinson Hospital, Sackler School of Medicine, Tel Aviv University, Petah Tiqva, Israel; Rosetta Genomics, Rehovot, Israel
Background: Although the prediction of malignant potential is usually straightforward in adrenocortical tumors (ACTs), some present with borderline features and elude specific diagnosis. Several protocols for ACT analysis have been suggested. The most reproducible is that of Weiss, who assessed 9 microscopic features thought to be related to malignancy. The presence of 3 or more of these features in a given tumor indicates malignant potential. However, some of the features show poor correlation between pathologists. Information on the molecular pathogenesis of the tumors is continuously accumulating but it has not been utilized thus far in the diagnostic setting. MicroRNAs are a family of short non-coding RNAs that play a central role in the regulation of gene expression and are strongly associated with tissue and cancer development. Prompted by the growing data on microRNA expression in a broad spectrum of neoplastic processes, we sought to examine microRNA expression in ACTs in an attempt to differentiate adrenocortical carcinomas (ACCs) from adrenocortical adenomas (ACAs).
Design: Thirty-four ACTs were retrieved from our files. Both clinical and macroscopic information (weight and diameter) were available. The nine histologic criteria of Weiss were evaluated in a blinded fashion, and tumors that met 3 or more were considered malignant. High quality RNA was extracted from tumor samples using proprietary protocols and profiled with Rosetta microRNA microarrays.
Results: Of the 34 ACTs, 8 were considered ACCs and 26 ACAs according to Weiss's criteria. Clinical data and patient follow-up supported the diagnosis in some of the cases. Microarray analysis revealed large and highly significant differences between ACCs and ACAs. Over a dozen microRNAs were up- or down-regulated in ACCs compared to ACAs, with 4- to 50-fold differences. The results demonstrated a high level of correspondence between Weiss's protocol and microRNA expression.
Conclusions: The strong correlation between Weiss's protocol of prognostic evaluation and the microRNA profile of ACTs imply that both accurately identify malignant ACTs. However, in borderline tumors, the addition of microRNA evaluation may greatly assist in predicting the biologic behavior of a given tumor and, thereby, in selecting the appropriate treatment.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 50, Tuesday Afternoon