Differential Expression of Dicer in Oncocytomas, Papillary, Clear Cell and Chromophobe Renal Cell Carcinomas
S Hooda, M Acquafondata, R Dhir, AV Parwani. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: MicroRNAs (miRNAs) are short 2022 nucleotides noncoding RNA molecules that negatively regulate gene expression at the posttranscriptional level. Dicer is a cytoplasmic RNAse III endonuclease involved in the production of mature miRNAs from longer primary transcripts. Dicer was shown to be up regulated in noninvasive precursor lesions of the lung and down regulated in the advanced adenocarcinoma of the lung. Although in prostate adenocarcinoma up regulation of Dicer was seen. In the present study, we evaluated the immunohistochemical expression of Dicer in tissue microarrays (TMAs) of the various kidney tumors.
Design: The TMA set consisted of 163 kidney tissue specimens arrayed onto slides in quadruplicate. Formalin-fixed paraffin-embedded blocks of renal clear cell carcinoma (56 cases), papillary carcinoma (25 cases), chromophobe carcinoma (22 cases) and oncocytoma (60 cases) were selected and marked after microscopic examination of the corresponding hematoxylin and eosin stained slides. One-millimeter cores were extracted from the marked areas and arrayed onto four recipient blocks. Immunohistochemistry was performed using anti-DICER1 antibodies. The non-neoplastic kidney adjacent to the areas of tumor served as internal positive control. The intensity of staining was scored from 0-3 (0= no staining, 1=weak, 2=moderate and 3=strong).
Results: A total number of 163 cases of kidney tissue were analyzed for immunoreactivity. Among these 82 cases of non-neoplastic kidney adjacent to the tumor showed an average immunoreactivity of 1.86 (range of 0-3) and 60 cases of oncocytomas showed an average intensity of 1.58 (range of 0-3). The different types of renal cell carcinomas showed down regulation of Dicer. The highest intensity was noted in papillary carcinomas (25 cases) with average intensity of 1.2 (range of 0-3), followed by chromophobe (22 cases) with an average intensity of 0.38 (range of 0-2) and clear cell carcinoma (56 cases) with an average intensity of 0.34 (range of 0-2).
Conclusions: Down regulation of Dicer was seen in malignant tumors of kidney compared to the nonneoplastic kidney and oncocytoma which is a benign tumor. It suggests that Dicer/miRNA might act as tumor suppressor. To our knowledge this is the first study analyzing the expression of Dicer in the kidney tumors. The Dicer/miRNA expression might be used to classify various renal tumors, to predict the prognosis and may form targets for future miRNA based cancer therapeutics.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 123, Monday Morning