HMGA2 in Early-Stage High-Grade Papillary Serous Carcinoma in Fallopian Tubes
J-J Wei. Northwestern University, Chicago, IL
Background: Before high-grade papillary serous carcinoma (HG-PSC) becomes invasive, it is believed to be a poorly defined short-lived precursor lesion. A recent characterization of serous tubal intraepithelial carcinoma (STIC) and of the p53 signature suggested that HG-PSC may follow a stepwise progression on cellular and molecular levels. HMGA2, an oncofetal protein, is overexpressed in ovarian cancer. The relationship between HMGA2 expression and p53 in the various stages of tumor progression in HG-PSC has never been tested.
Design: To test whether HMGA2 can be another valuable marker for STIC, we examined HMGA2 expression in 3 groups of patients: (1) 24 patients with STIC and its invasive counterpart, HG-PSC of the fallopian tubes, (2) 24 patients with HG-PSC of the ovaries but without STIC (positive control), and (3) 30 patients with cancer and normal fallopian tubes (negative control). The purpose of the study is to characterize whether HMGA2 can be a valuable marker complementary to p53 in detection of precursor or early serous carcinoma arising from fallopian tube. Our goal is to establish a link of HMGA2 with tumorigenesis of high grade serous carcinoma and identify a tool for the diagnosis of early ovarian cancer.
Results: We found that HMGA2 was overexpressed in 75% of patients with STIC, was coexpressed with p53 in more than 50% of patients, and was completely negative in the secretory cells of the 30 patients with normal fallopian tubes. Among 7 patients with cells negative for p53 staining, HMGA2 was positive in 5; among 6 patients whose tumor cells were negative for HMGA2 in STIC, 3 were positive for HMGA2 in the invasive component; about 70% of invasive HG-PSC tumor cells were immunoreactive for both HMGA2 and TP53. In invasive carcinoma, HMGA2 overexpression was correlated with p53 (r = 0.45), indicating the role of HMGA2 in p53 mediated tumor progression.
Conclusions: Our findings of immunoreactivity for HMGA2 in both STIC and invasive PSC may 1) lead to a novel, useful biomarker to complement p53 in the detection of early-stage serous carcinoma; 2) provide a new avenue for the study of the role of HMGA2 in the tumorigenesis of HG-PSC.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 149, Tuesday Afternoon