Differential microRNA Expression Signatures in Salivary Duct Carcinomas Versus Her2/Neu 3+ Positive Hormone Receptor Negative Invasive Ductal Breast Carcinomas and High Grade Breast Ductal Carcinoma In Situ
Stefan Costinean, Arianna Bottoni, Luciano Cascione, Theodoros Teknos, Enver Ozer, Matthew Old, Amit Agrawal, Carlo M Croce, Hans Iwenofu. The Ohio State University, Columbus
Background: Salivary duct carcinomas (SDC) are highly lethal tumors that are histologically and immunohistochemically indistinguishable from invasive high grade Her2/Neu positive hormone receptor negative ductal breast carcinomas (IDBC). MicroRNAs (miRs)s are a newly discovered class of noncoding RNAs with roles in posttranscriptional regulation. Emerging data in hematologic and solid tumors indicate that there are miR expression “genetic signatures” that could be used for diagnosis, prognosis or therapy.
Design: We investigated whether the common histopathologic and immunophenotypic features of SDC and Her2/Neu 3+ hormone receptor negative IDBC correspond to a similar miR "signature". 5 cases of SDC, 6 cases of IDBC Her/neu2 3+ and 4 cases of high grade ductal breast carcinoma in situ (DCIS) were selected from paraffin embedded blocks from the OSU tissue archive. Representative areas of tumor were cored. RNA was isolated with Recover easy from Ambion and analyzed using Nanostring technology. The results were processed using SAM and cluster analysis module. To validate Nanostring results TaqMan Assays were used. The comparative CT method for relative quantitation of gene expression was used to determine miR expression levels.
Results: The expression patterns of Her2/Neu 3+ IDBC and SDC were strikingly similar and much less so with high grade DCIS. We found that compared to SDC, Her/neu3+ IDBC had higher levels of miR142-3p and miR10a. When compared to SDC, DCIS had higher levels of miR10a also, together with miR99a, miR335 and miR331-3p and lower levels of miR19a and miR15a. All results were validated by Real Time PCR.
Conclusions: A striking conclusion was that SDCs are closer to Her2/neu 3+ IDBC than the high grade DCIS. Only 2 miRs were differentially expressed compared to IDBC and 4 miRs differentially expressed compared to the high grade DCIS. One of the miRs differentially expressed - miR10a - was consistently higher in both high grade DCIS and Her2/Neu 3+ IDBC compared to the SDCs suggesting that this miR is breast specific and its expression is increased early in tumorigenesis.
Category: Head & Neck
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 195, Monday Morning