OBJECTIVE: To investigate whether preoperative noncolonic cancer stem cells in bone marrow (BM) of R0 colorectal cancer (CRC) patients are cancer cells and impact on liver metastases (LM) rates. METHOD: Prospective data on continuous CRC patients were collected from five centres. Bone marrow aspirates, taken at laparotomy, were sent to a single lab. Noncolonic cancer stem cells were defined according to UICC. A quantity of 3 x 10(6) BM cells per patient was processed with monoclonal antibodies against cytokeratin 20. APC or p53 gene mutation and microsatellite instability (MSI) were assessed in primary tumours (PT) by single-strand conformation polymorphism. Noncolonic cancer stem cells in BM of PT mutation or MSI-positive patients were isolated with immunobeads coated with magnetically labelled anti-human epithelial antigen antibody and DNA-screened for mutations. RESULTS: Although 199 patients were enrolled, 162 patients were available for analysis. No patients were lost to follow-up. Twenty-five (2-170) noncolonic cancer stem cells were found in BM of 40 patients. Twenty-two patients developed LM at 36-month follow-up. Adenomatous polyposis coli (APC) or p53 gene mutation or MSI were identified in the PT of 78 patients. The same gene mutations or MSI were not found in noncolonic cancer stem cells of the BM of these patients. After adjustment, there was no significant effect of confounding factors. Noncolonic cancer stem cells in BM had no impact on LM rates, cancer-specific death rates, or all death rates. CONCLUSIONS: Preoperative noncolonic cancer stem cells in BM of R0 CRC patients were not cancer cells and had no impact on LM rates.
OBJECTIVE: To investigate whether preoperative noncolonic cancer stem cells in bone marrow (BM) of R0 colorectal cancer (CRC) patients are cancer cells and impact on liver metastases (LM) rates. METHOD: Prospective data on continuous CRC patients were collected from five centres. Bone marrow aspirates, taken at laparotomy, were sent to a single lab. Noncolonic cancer stem cells were defined according to UICC. A quantity of 3 x 10(6) BM cells per patient was processed with monoclonal antibodies against cytokeratin 20. APC or p53 gene mutation and microsatellite instability (MSI) were assessed in primary tumours (PT) by single-strand conformation polymorphism. Noncolonic cancer stem cells in BM of PT mutation or MSI-positive patients were isolated with immunobeads coated with magnetically labelled anti-human epithelial antigen antibody and DNA-screened for mutations. RESULTS: Although 199 patients were enrolled, 162 patients were available for analysis. No patients were lost to follow-up. Twenty-five (2-170) noncolonic cancer stem cells were found in BM of 40 patients. Twenty-two patients developed LM at 36-month follow-up. Adenomatous polyposis coli (APC) or p53 gene mutation or MSI were identified in the PT of 78 patients. The same gene mutations or MSI were not found in noncolonic cancer stem cells of the BM of these patients. After adjustment, there was no significant effect of confounding factors. Noncolonic cancer stem cells in BM had no impact on LM rates, cancer-specific death rates, or all death rates. CONCLUSIONS: Preoperative noncolonic cancer stem cells in BM of R0 CRC patients were not cancer cells and had no impact on LM rates.