Detection of Lymph Node Involvement by Cytokeratin Immunohistochemistry is an Independent Prognostic Factor After Curative Resection of Esophageal Cancer

Involved lymph nodes (LN) are a negative prognostic factor in esophageal cancers. To assess the role of nodal micrometastases, we performed immunohistochemical analyses of LN after resection of node-negative esophageal cancers and correlated the results with survival. Seventy patients with esophageal cancer after curative resection and conventionally negative nodes were included. The LN were examined with six consecutive sections (three hematoxylin and eosin (HE) stained and three stained immunohistochemically with the cytokeratin (CK) antibodies AE1/AE3). Survival was evaluated uni- and multivariately. Median follow-up was 4.1 years. Immunohistochemical analysis showed CK-positive LN in 16 (23%) patients. Of those 16 cases with CK-positive LN, nine had aviable macrometastases, ten had CK-positive scars/fibrosis and five had viable micrometastases. All patients with aviable macrometastases or CK-positive scars/fibrosis had undergone neoadjuvant chemoradiation. Five-year survival was 48% in all patients. In univariate analysis, survival was worse in patients with CK-positive LN (5-year survival of 30% vs. 54% in CK-negative LN; p < 0.02) and in patients with squamous cell carcinoma (5-year survival of 38% vs. 75% in adenocarcinoma; p = 0.05). Multivariate analysis revealed CK-positive LN (p = 0.02) and (borderline) squamous cell carcinoma (p = 0.06) as negative prognostic factors. The immunohistochemical analysis of LN may detect (viable or non-viable) tumor cells in lymph nodes after resection of conventionally node-negative esophageal cancers. Conventional pathological analysis by HE, therefore, understages esophageal cancer in these cases. The detection of CK-positive cells in resected LN is an independent prognostic factor in otherwise LN-negative esophageal cancer.