Detection of microRNA-21 Expression in Pregnancy-Associated Breast Cancer: A Possible Marker of Poor Prognosis
S Gomez-Macias, BA Walter Rodriguez, VA Valera Romero, M Sobel, MJ Merino. Autonomous University of Nuevo Leon, Monterrey, Mexico; National Cancer Institute, National Institutes of Health, Bethesda
Background: miRNAs are small fragments of non-coding RNAs that are involved in the regulation of gene expression. Recent studies have shown that specific microRNAs can act as key modulators of tumorigenesis. Specifically, miR-21 overexpression has been suggested to play an important role in the development and progression of breast cancer (BC). The existence of specific miRNAs in pregnancy-associated breast cancer (PABC) is not known. We evaluated the presence of miR-21 in cases of PABC, compared the expression with regular BC and correlated with known prognostic factors.
Design: A total of 35 patients, 25 PABC and 10 cases with similar clinicopathological features but not pregnancy associated were analyzed for miR-21 expression by RT-PCR. MicroRNAs surrounding miR-21 (miR-301, miR-10a and miR-633) were also evaluated to confirm the specificity of the results for the miR-21. We then analyzed protein expression by IHC for potentially targeted genes, including PTEN, Bcl-2 and PDCD4, and finally correlated the results with patient's clinico-pathological features.
Results: Patient's mean age was 35 yrs. Lymph node metastasis was present in 75% of cases. All tumors were infiltrating ductal carcinomas; 32 % were histologic grade 2 and 68% were grade 3. In the PABC cases compared with the control group, positive ER status was seen in 19% vs 37% of patients, 62.5% were negative for PR in all cases and 100% vs 66.7% were HER-2 negative. We found overexpression of miR-21 in all tumor samples compared with their own normal adjacent tissue. Overexpression was significantly correlated with high histological grade, but not with lymph node status or the presence of advanced disease. PTEN protein expression was negative in 80% of the cases, PDCD4 expression was cytoplasmic positive in 75% of the cases and 60% of tumors were negative for Bcl-2. PTEN negative expression was significantly correlated with increase of miR-21 (p=0.044).
Conclusions: Our results demonstrate important miR-21 overexpression in PABC. Changes in target genes such as PTEN and Bcl-2 support the concept that miR-21 may play an important oncogenic role in breast cancer in general. Expression of this miRNA may be a possible indicator of poor prognosis in breast cancer.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 16, Wednesday Afternoon