Expression of Tissue Factor and Heparanase in Endometrial Clear Cell Carcinomas: Clinicopathologic Significance and a Possible Role for Tissue Factor in Thromboembolic Events.
Oluwole Fadare, Idris Renshaw, Sharon X Liang. Vanderbilt University, Nashville; Vanguard Pathology, Austin; Long Island Jewish Medical Ctr, New Hyde Park
Background: Preliminary analyses suggest that patients with endometrial clear cell carcinoma (CCC) may have an increased risk for thromboembolic events [TVE]. Tissue factor (TF) and heparanase (Hep) are 2 proteins that are involved in activation of the coagulation cascade and several aspects of tumor progression. Hep may also induce TF expression. The purpose of this study is to assess the clinicopathologic significance of TF and Hep expression, especially as they relate to the risk of TVE, in CCC and selected other endometrial cancers
Design: 84 endometrial carcinomas, including 17 CCC, 20 serous carcinomas (SC), 15 grade 1 endometrioid carcinomas (g1-EC), 15 grade 2 EC (g2-EC), 10 grade 3 EC (g3-EC), and 7 mixed carcinomas with at least a 10% clear cell component (mixed CCC), were evaluated for the expression of Hep and TF by immunohistochemistry, and their associated frequency of TVE
Results: 7 of 84 patients experienced 8 TVE during the follow-up period. On univariate analysis, CCC (4/17 cases) was more likely to be associated with a TVE than all other carcinomas (3/67 cases, p=0.03). On multivariate analysis, the CCC histotype (OR 5.2, 95% CI 2.4523-13.6754, p=0.026) was significantly associated with an elevated risk for TVE. TF expression was present in 12 (14.28%) of 84 endometrial carcinomas, including in 41% of CCC, 10% of SC, 14% of mixed CCC, 13% of g1-EC, and in 0% of grade 2 and 3 EC. TF expression was significantly more likely to be seen in CCC than all other cancers (p=0.0018) and all other high grade cancers (p=0.007). On multivariate analysis, TF expression was significantly associated with the risk of TVE (OR 4.8, 95% CI 1.9196-11.93, p= 0.013). TF expression was not associated with patient outcome or any other clinicopathologic parameter. Hep expression was present in 57 (67.8%) of 84 endometrial carcinomas, including 59% of CCC, 43% of mixed CCC, 25% of SC, 100% of g1-EC, 100% of g2-EC, and in 90% of g3-EC, and was significantly associated with the endometrioid histotype, myometrial and lymphovascular invasion, but not outcome or the risk of TVE. For the overall group, there was no significant correlation between Hep and TF expression (Spearman rank correlation, r = 0.311, p=0.4)
Conclusions: Patients with CCC have an increased risk of developing TVE as compared with patients with the other histotypes. This increased risk may be related, at least in part, to an increased rate of TF expression in CCC.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 169, Wednesday Afternoon