Prognostic influence of immunohistochemically detected lymph node micrometastasis and histological subtype in pN0 oesophageal cancer

INTRODUCTION: Differences in frequency and clinical impact of lymph node micrometastasis between histological subtypes of oesophageal cancer have not been determined. METHODS: 1204 lymph nodes from 32 squamous cell carcinomas and 54 adenocarcinomas with complete resection and pN0 status were re-evaluated using a serial sectioning protocol including immunohistochemistry. Intra-nodal tumour cells were classified as micrometastases (0.2-2 mm) or isolated tumour cells (>0.2 mm). RESULTS: There was no significant difference in the frequency of micrometastases between adenocarcinoma and squamous cell carcinoma (11.3% vs. 3.1%, p=n.s.). In the squamous cell carcinoma group, Kaplan-Meier curves showed a significantly prolonged 5-year survival (p=0.02) and disease free interval (p>0.01) for immunohistochemically node negative versus node positive patients. In patients with adenocarcinoma, no such difference (p=n.s. and p=n.s., respectively) was seen. In patients who did not undergo pre-treatment, those with adenocarcinoma had a significant 5-year survival (65% vs. 53%; p=0.03) and disease free interval (83% vs. 58%; p>0.05) advantage over those with squamous cell carcinoma. After pre-treatment, no difference between the histological subtypes was detected. Regression analysis did not reveal any factors that significantly affected overall survival in node negative patients. However, four factors did significantly influence disease free interval: pre-treatment (HR 3.3 [95% CI 1.2-9.1], p=0.02); micrometastasis (HR 5.3 [95% CI 1.4-19.7], p=0.01); UICC stage II vs. 0/I (HR 2.2 [95% CI 1.1-4.4], p=0.03); and adenocarcinoma (HR 0.3 [95% CI 0.1-0.9], p=0.03). CONCLUSION: The difference in frequency and clinical impact of immunohistochemically detected micrometastasis may indicate that adenocarcinoma and squamous cell carcinoma should not be treated as one entity.