Cytokeratin staining of resected lymph nodes may improve the sensitivity of surgical staging for endometrial cancer

Objectives The presence of metastases to regional lymph nodes (LN) is the single most important risk factor in endometrial cancer. Advances in molecular biology have provided more sensitive methods for detecting micrometastasis. This was a pilot study to determine whether cytokeratin staining of LN from endometrial cancer patients is more sensitive than traditional histopathologic evaluation for the detection of micrometastasis. Methods The inclusion criteria included patients with surgical stage I-II endometrial cancer having >50% myometrial invasion, lesions >2 cm, and negative LN together with one of the following: FIGO grade 3 or cervical or lymph-vascular involvement. A matched control group included patients with LN metastasis. The evaluation of the LN at the time of initial surgery consisted of a frozen section and a reevaluation on permanent sections with H&E. In the study, lymphadenectomy specimens were cut, stained again with H&E and with cytokeratin, and examined. Cytokeratin staining was performed with AE1/AE3 antibodies. There were 16 LN-negative cases and 9 LN-positive controls. Results There was complete agreement between the LN assessment at time of surgery and the study H&E review prior to the staining for cytokeratin. However, 2 LN-negative cases (12.5%) had micrometastasis by cytokeratin staining. One of these patients developed recurrent disease in the para-aortic LN and died of disease at 2.8 years. Conclusion Cytokeratin staining may improve the sensitivity for detection of metastasis compared to traditional evaluation. This study strongly suggests that these micrometastasis are clinically significant. An approach incorporating cytokeratin analysis could improve the risk assessment of specific patients.