Clinical Value of Immunohistochemically Detected Lymphatic and Vascular Invasions in Clinically Staged Endometrioid Endometrial Cancer

Abstract

A novel technique to differentiate lymphatic from vascular invasion and to assess the clinicopathological significance in patients with early endometrial cancer. Dual immunohistochemical techniques against pancytokeratin epithelial cell marker (PCK), D6 lymphatic endothelial marker, and CD31 nonspecific endothelial marker were deployed for differentiation. Seventy-seven patients were included with a median follow-up of 161 months. Tumors with positive evidence of lymphovascular space invasion on PCK-CD31 immunohistochemistry and absence of lymphatic space invasion on PCK-D6 were regarded as cases with vascular space invasion only. Significant association between depth of myometrial invasion, recurrence rate, and hematoxylin and eosin that detected lymphovascular space invasion were noted (P < 0.0001 and P = 0.009, respectively). The 5-year recurrence-free survival was 45% for the group with hematoxylin and eosin evidence of lymphovascular space invasion compared with 89% for the group without (P = 0.0014). Pancytokeratin epithelial cell marker-D6 dual immunostaining detected lymphatic space invasion in 22 (29%) patients. There was significant association between lymphatic space invasion and depth of myometrial invasion (P = 0.046). Lymphatic space invasion detected on immunohistochemistry was present in 8 (72%) of 11 patients with recurrent disease. Of the remaining 49 patients with no evidence of recurrent disease, only 11 (22%) had presented with lymphatic space invasion. Positive association between tumor recurrence rate and lymphatic space invasion was noted (P = 0.003). The 5-year recurrence-free survival was 53% for the group with lymphatic invasion compared with 93% for the group without. This difference was similarly shown to be of significance (P = 0.0009). There were no apparent association between immunohistochemically detected lymphovascular or vascular space invasion and any clinicopathological factor. Lymphatic space invasion detected by using dual immunostaining is of significant value in identifying high-risk patients.