Inzidenz und prognostische Bedeutung von okkult frühdisseminierten Tumorzellen in Lymphknoten bei Patienten mit resektablem Pankreaskarzinom

Abstract

Occurrence of tumor relapse is frequent in patients with pancreatic cancer despite the absence of residual tumor detectable at primary surgery [1-4]. Therefore it has to be assumed that current tumor staging procedures fail to identify minimal amounts of tumor cells disseminated to secondary organs, which might be precursors of subsequent metastatic relapse. In the present study we examined lymph nodes judged as „tumor-free“by routine histopathology from 85 pancreatic cancer patients without overt métastases (M0) who had undergone intentional curative tumor resection. Isolated tumor cells were detected by immunohistochemistry with the monoclonal antiepithelial antibody Ber-EP4. In total 47 (55.3%) of these 85 patients displayed Ber-EP4+ cells in „tumor-free“ lymph nodes. No significant correlations were found between immunohistochemical lymph node status and primary tumor status (pT), pathohistological lymph node status (pN) or tumor grading (G). Postoperative Kaplan-Meier survival analyses revealed that patients with Ber-EP4+ cells in „tumor-free“ lymph nodes had both a significantly reduced relapse-free survival (p = 0.001) and overall survival (p = 0.002). Furthermore, multivariate Cox regression analysis confirmed the presence of Ber-EP4-f cells in „tumor-free“ lymph nodes as an independent prognostic factor for a significantly reduced relapse-free survival (relative risk: 3,2; 95% CI: 1,561 - 566,699; p = 0,002) and overall survival (relative risk: 3,630; 95%CI 1,733 - 737,605; p = 0.001). The frequent occurrence and prognostic impact of early disseminated tumor cells in lymph nodes of patients with operable pancreatic cancer support the need for a refined staging system of excised lymph nodes, which should include immunohistochemical examination.