microRNA Expression Profiling in Prostate Cancer: Possible Role as a Biomarkers and/or Molecular Therapy.
Beatriz A Walter Rodriguez, Maria P Vargas, Vladimir A Valera Romero, Mark Sobel, Peter Pinto, Maria J Merino. National Cancer Institute, Bethesda; NCI/NIH, Bethesda
Background: miRNAs are small non-coding RNA molecules that have been shown to regulate the expression of genes linked to cancer. The relevance of miRNAs in the development, progression and prognosis of prostate cancer is not fully understood. It is also possible that these specific molecules may assist in the recognition of aggressive tumors and the development of new molecular targets. Our study investigated the importance of several miRNAs in cases of prostate cancer and correlated them with clinicopathological parameters.
Design: A total of 114 samples from 37 prostate cancer patients were manually microdissected to obtain pure populations of tumor cells, normal epithelium and adjacent stroma. miRNA was extracted for PCR array profiling. Differentially expressed miRNAs for each case comparing tumor vs. normal epithelium and tumor-adjacent stroma samples were defined as those with a two-fold change and a p value <0.001. All the cases were histologically reviewed and the grade, presence of extracapsular, perineural, seminal vesicle and lymphatic invasion was recorded to further evaluate them as prognostic factors.
Results: Patients' mean age was 57 years. Five patients were histologically Gleason score 6, 20 had Gleason score 7 (3+4) and 12 Gleason score 8 or higher. Two patients had clinical stage T2a, 1 T2b, 25 T2c, 7 T3a and 1 case T3b. Three cases had positive lymph nodes. Loss of 18 miRNAs (e.g.miR34c, miR29b, miR212 and miR10b) and upregulation of miR143 and miR146b were significantly found in all the tumors in comparison with normal epithelium and/or stroma (p≤ 0.001). A different signature was found in the high grade tumors (Gleason score ≥ 8) when compared with tumors Gleason score 6. Upregulation of miR122, miR335, miR184, miR193, miR34, miR138, miR373, miR9, miR198, miR144 and miR215 and downregulation of miR96, miR222, miR148, miR92, miR27, miR125, miR126, miR27 was found in the high grade tumors. miR193b and 181b, miR20a and 10b, and miR125a and 155 were differentially expressed in patients having perineural (PI), extracapsular (ECI) and lymphatic invasion, respectively.
Conclusions: miRNA profiling in prostate cancer appears to have unique and different expression patterns, in low and high grade Gleason tumors. A miRNA signature was also found correlated to poor prognostic factors such as ECI, PI and lymphatic involvement. These differential expressed miRNAs may provide novel diagnostic and prognostic tools that will assist in the recognition of prostate cancers with aggressive behavior.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 99, Monday Morning