Detection of micrometastasis in bone marrow of pancreatic cancer patients

Design: Here we applied an immunocytochemical cytokeratin assay that allows the identification of individual pancreatic carcinoma cells disseminated t o bone marrow. Patients and methods: Prior to therapy, bone marrow was aspirated from the upper iliac crest of 48 patients with ductal adenocarcinoma of the pancreas at various disease stages as well as an age-matched control group of 33 no n-carcinoma patients. Tumor cells in cytologic bone marrow preparations wer e detected with monoclonal antibodies (mAbs) CK2, KL1 and A45-B/B3 to epith elial cytokeratins (CK), using the alkaline phosphatase anti-alkaline phosp hatase method. Results: CK+ cells were found in 25 (52.1%) of 48 cancer patients. The over all frequency of these cells was 1 to 85 per 5x 10(6) mononuclear cells. 4 (8.3%) cancer patients had specimens that stained with the mAb CK2, compare d with 16 (33.3%) patients who displayed KL1+ cells and 9 (18.6%) patients who showed A45-B/B3+ cells. After a median follow up of 22.8 (range 3-48) m onths, the occurrence of tumor relapse was significantly associated with th e outcome of the immunocytochemical screening before the time of primary su rgery. 6 (40.0%) out of 15 patients who underwent complete surgical resecti on but had tumor cells in bone marrow presented with distant metastasis and 7 (46.7%) with local relapse as compared to none of 12 corresponding patie nts without such cells (p< 0.02). Univariate survival analysis revealed tha t the presence of CK+ cells in bone marrow was predictive of reduced overal l survival (p<0.03). Conclusions: Anti-CK mAbs are reliable probes for the immunocytochemical de tection of single pancreatic cancer cells disseminated to bone marrow. Thus the described technique may help to identify patients with pancreatic canc er and potential high risk of early metastic relapse. The results promise t o be of important assistance in determining prognosis and consequences in t herapy of early stage pancreatic cancer.