Occult lymph node metastases detected by cytokeratin immunohistochemistry predict recurrence in node-negative endometrial cancer

Objective. Even after curative resection of early endometrial cancer, some patients die as a result of recurrence. We believe that these patients like ly had occult lymph node metastases at the time of diagnosis. In an attempt to identify the responsible occult metastases, the clinicopathological sig nificance of cytokeratin expression in lymph nodes with unconfirmed metasta sis was evaluated retrospectively in patients with endometrial carcinoma. Methods. We examined 304 pelvic lymph nodes and 46 primary tumors excised f rom 46 patients with endometrial cancer, including 36 with Stage I disease and 10 with Stage IIIc disease. Formalin-fixed paraffin-embedded tissue sec tions were stained immunohistochemically using antibodies against cytokerat in, CA125, and macrophage-related antigen. Sections were also stained with hematoxylin and eosin. Results. In 10 patients with Stage IIIc disease, cytokeratin expression was detected in cells other than the tumor cells in all 13 lymph nodes with me tastasis and also in 20 (30.3%) of 66 lymph nodes without metastasis. Cytok eratin expression was observed in 37 (16.4%) of 225 lymph nodes with unconf irmed metastasis, which were obtained from 14 of 36 patients with Stage I d isease. Five of fourteen patients with lymph nodes expressing cytokeratin h ad recurrent disease in the pelvic cavity, while all 22 patients with uncon firmed cytokeratin expression in their lymph nodes showed no recurrence. Cy tokeratin and CA125 were detected simultaneously on macrophages in lymph no des. Cytokeratin expression in lymph nodes was closely related to lymph-vas cular space involvement of the primary tumor, but was not related to either histological grade or depth of myometrial invasion. Multivariate analysis identified cytokeratin expression as an independent risk factor for recurre nce in Stage I endometrial cancer. Conclusions. The immunohistochemical expression of cytokeratin in lymph nod es with undetected metastases predicts occult metastasis to these nodes and is a risk factor for recurrence in early-stage endometrial cancer. (C) 200 1 Academic Press.