Significance of Cytokeratin Fragment M65 and Cytokines IL6, IL8 and IL17A in Bone Marrow Aspirates of Colorectal Cancer Patients

Abstract

Aims: Soluble cytokeratin (CK) fragments and inflammatory interleukins (ILs) in bone marrow (BM) aspirates of colorectal cancer (CRC) patients are expected to indicate presence of disseminated tumor cells (DTCs) and anticancer response of the host, respectively. The present study investigated the relations of CK18 fragment M65, IL6, IL8, and IL17A in BM samples to the presence of DTCs and prognosis. Place and Duration of Study: Department of Medicine (Medical Unit II) and Department of Surgery, Donauspital Vienna, between 2002 and July 2005. Methodology: BM aspirates were obtained immediately prior to and one and two years after tumor surgery, respectively, and M65 and cytokines were quantified by ELISA assays. Results: 16/66 patients revealed tumor-positive BM aspirates, and 10/46 evaluable patients relapsed within five years. M65 levels exhibited no relation to either positive biopsies, relapses or methylation status of O6-methyl guanine methyl transferase (MGMT). In contrast, IL17A concentrations of BM aspirates were elevated in non-relapsed versus relapsed, as well as MGMT-wildtype versus MGMT-methylated patients. Due to large individual variations, IL6 and IL8 levels of BM showed no significant differences for non-relapsed versus relapsed patients. Conclusion: M65 levels of BM samples of CRC patients exhibited no correlation with micrometastases or disease recurrence, respectively; however, patients who achieved disease-free survival revealed increases of IL17A in BM aspirates, possibly indicating immune response to tumor cells.