Tumor involvement of locoregional lymph nodes (LN), as detected during routine histological examination, is an established negative prognostic factors in resected esophageal cancers. Recurrence or understaging, however, frequently occurs as a consequence of previously undetected tumor cells. In this study we, therefore, performed immunohistochemical analyses of LN after resection of 70 formally node negative esophageal cancers and correlated the results with long-term survival.
Methods: Seventy cases of esophageal cancer (50 squamous cell carcinoma, 20 adenocarcinoma; 79% male; 74% neoadjuvant chemoradiation) who had (by conventional histology) a curative resection with negative margins and no LN involvement were included in our study. The LN were examined with six consecutive sections (thickness 2 µm, distance 150 µm). Three sections were hematoxylin-eosin (HE) -stained, the three others were stained immunohistochemically with the cytokeratin (CK)-antibodies AE1/AE3. The definition of micrometastases was performed as suggested by Hermanek et al. in 1999. Long-term survival was evaluated by the Kaplan-Meier-method (univariately) and Cox-regression-analysis (multivariately).
Results: Immunohistochemical analysis showed CK-positive LN in 16 of the 70 (23%) patients. Micrometastasis were found in five of these 16 cases. Five-year survival was 45% in all patients. In univariate analysis survival was worse in patients with CK-positive LN (31% vs. 49% in CK-negative LN; p=0.01) and in patients with squamous cell carcinoma (36% vs. 77% in adenocarcinoma; p<0,02). Multivariate survival analysis revealed CK-positive LN (p=0.03) and squamous cell carcinoma (p<0.04) as independent prognostic factors. The T-stage, a neoadjuvant chemoradiation and the response to neoadjuvant chemoradiation did not influence survival rates.
Conclusions: The immunohistochemical analysis of LN may detect (vital or non-vital) tumor cells in LN after resection of conventionally node-negative esophageal cancers. Conventional HE pathological analysis, 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.