Immunzytochemischer nachweis und prognostische bedeutung von epithelialen tumorzellen im knochenmark bei patienten mit pankreaskarzinomen

Introduction: Minimal residual disease in patients with operable pancreas carcinoma is frequently missed by current non-invasive tumor staging. Purpose: We applied an immunocytochemical cytokeratin assay that allows the identification of individual pancreas carcinoma cells disseminated to bone marrow. Methods: Prior to therapy bane marrow was aspirated from the upper iliac crest of 42 patients with pancreas carcinoma and a control group of 30 non-carcinoma patients. Tumor cells in cytologic bone marrow preparations were detected with monoclonal antibodies (mAbs) CK2, KL1 and A45-B/B3 to epithelial cytokeratins (CK), using the APAAP-method. Results: CK-positive cells were found in 14 (58.3%) of 24 cancer patients treated in curative intent and 10 (55.6%) of 18 patients with extended disease. After a mean follow up of 12.7 (3-32) months, 6 (42.8%) out of 14 patients who underwent complete surgical resection presented with tumor relapse and 5 (35.7%) with distant metastases as compared to none of 10 corresponding patients without such cells (p<0.04). Moreover, patients with epithelial tumor cells in bone marrow showed also a significantly shorter overall survival than those without tumor cells (p<0.03). Conclusion: Immunocytochemical screening for epithelial tumor cells in bone marrow might contribute to an improved staging and is of prognostic relevance for pancreas carcinoma patients.