Significant Overexpression of HMGAs in Serous Ovarian Carcinoma in Association with p53
A Mahajan, L Gellert, XJ Yang, J Wei. Feinberg School of Medicine, Northwestern University, Chicago, IL; New York University, New York, NY
Background: HMGA1 and 2, high-mobility-group AT-hook proteins, are important regulators of cell growth, differentiation, apoptosis and transformation. Overexpression of HMGA1 and 2 has been reported in human ovarian cancer. Furthermore, HMGA2 overexpression was identified in early stage of ovarian cancer in animal models. Ovarian cancer is genetically and histologically heterogeneous. To further characterize whether HMGAs are the important molecules in association with the tumorigenesis of specific type ovarian cancer, and with p53 mutation, we initiated this study.
Design: A total of 60 cases with ovarian carcinoma were collected. Among them 30 were high grade papillary serous (PSC) and 30 endometrioid (EMC). Case matched normal tissues from fallopian tube and endometrium were used as controls. All PSC were FIGO grade 3. EMC was confirmed to be ovarian primary. Expression of HMGA1, HMGA2 and p53 were examined by immunohistochemistry (IHC). Semiquantitative immunoscores were scaled by immunointensity and percentage.
Results: There were significant differences of HMGA1 and 2 between high grade PSC and EMC in ovary. In PSC, overexpression of HMGA1 and HMGA2 was identified in 72% and 58%, respectively. In contrast, expression of HMGA1 and 2 was detected in only 44% and 17% in EMC. When we compared HMGA1 and 2 expressions with p53, a correlation of HMGA overexpression with p53 in PSC was found (r=0.54, r=0.38 respectively).
Conclusions: This is the first study to examine HMGA expression in different histological types of ovarian cancer. We found overexpression of HMGAs is significantly higher in PSC than that in EMC. Particularly, overexpression of HMGAs is correlated with p53 overexpression. Findings further support the functional roles of HMGAs in p53 mediated tumorigenesis.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 159, Monday Morning