Micrometastases in bone marrow: Prognostic indicators for pancreatic cancer

Minimal residual disease in patients with operable pancreatic carcinoma is frequently missed by current noninvasive tumour staging. We applied an immu nocytochemical cytokeratin assay that allows identification of individual p ancreatic carcinoma cells disseminated to bone marrow. Prior to therapy, bo ne marrow was aspirated from the upper iliac crest of 48 patients with duct al adenocarcinoma of the pancreas at various disease stages and an age-matc hed control group of 33 noncarcinoma patients. Tumor cells in cytologic bon e marrow preparations were detected,vith monoclonal antibodies (mAbs) CK2, KL1, and A45-B/B3 to epithelial cytokeratins (CK) using the alkaline phosph atase antialkaline phosphatase method. CK-positive cells were found in 14 ( 48.4%) of 31 cancer patients treated with curative intent and in 10 (58.8%) of 18 patients with extended disease. The overall frequency of these cells was 1 to 83 per 5 x 10(5) mononuclear cells with no significant difference s between patients at different tumor stages and lymph node involvement. Af ter a median follow-up of 22.8 months (range 3-48 months), 6 (40.0%) of 15 patients who underwent complete surgical resection but had tumor cells in b one marrow presented with distant metastasis and 7 (46.7%) had local relaps e compared to none of 12 corresponding patients without such cells (p < 0.0 5). Univariate survival analyses revealed that the presence of CK-positive cells was predictive of reduced overall survival. In conclusion, anticytoke ratin mAbs are reliable probes for the immunocytochemical detection of sing le pancreatic cancer cells disseminated to bone marrow. Thus the described technique may help identify patients with pancreatic cancer and at potentia lly high risk of early metastatic relapse. The results promise to be of imp ortant assistance for determining prognosis and the consequences in therapy of early stage pancreatic cancer.