High Mobility Group A1 (HMGA1) Proteins Associate with ER-Negativity and High Nuclear Grade in Breast Cancer in a Cohort of Asian Women
Rebecca J Asch, Ashley Cimino-Mathews, Leslie Cope, Alan Meeker, Young K Bae, Linda MS Resar. Johns Hopkins University School of Medicine, Baltimore, MD; Johns Hopkins University School of Medicine, Baltimore, Korea; Yeungnam University College of Medicine, Daegu, Korea
Background: Breast cancer remains a leading cause of death in women worldwide. Here, we investigate HMGA1 immunoreactivity as a biomarker for more advanced disease in a cohort of Asian women with breast cancer. HMGA1 encodes the HMGA1a/1b chromatin remodeling proteins, which function in regulating gene expression.HMGA1 is highly enriched in embryonic stem cells and some high-grade tumors with poor outcomes. We focused on Asian women because they present at a younger age and with a more advanced stage than other women with breast cancer, suggesting that HMGA1 could be important in tumor progression in these women.
Design: Tissue microarrays (TMAs) were generated from paraffin-embedded tissue sections. HMGA1 protein levels were assessed by immunohistochemistry. TMAs contained cores from 594 primary tumors from a Korean cohort with detailed histopathologic and clinical data (tumor grade, stage, metastases, survival, ER/PR/HER-2, P-cadherin status). Normal tissues were included as controls. Positive staining was identified as nuclear immunoreactivity and was scored using a 3 point scale based on the product of staining intensity (weak =1, moderate =2, strong =3) and staining extent (% of positive cells; <30% =1, 30-60% =2, >60% =3). The highest score per case was used for subsequent analyses.
Results: HMGA1 immunoreactivity was observed in 515 of 594 cases of primary breast tumors, with intensity scores ranging from 0-3. Of positive cases, the immunoreactivity score was <3 in 64 (12%), 3-6 in 215 (42%) and >6 in 236 (46%). There was a significant, positive correlation between HMGA1 staining and ER-negativity. In addition, HMGA1 levels correlated positively with advanced nuclear grade.
Conclusions: We demonstrate for the first time that HMGA1 correlates with both ER-negativity and advanced nuclear grade in primary tumors from Korean women with breast cancer. Although further studies are needed, our results suggest that HMGA1 contributes to tumor progression and could represent a useful biomarker and effective therapeutic target.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 14, Monday Morning