Bone Marrow Cytokeratin 19 MRNA Level is an Independent Predictor of Relapse-free Survival in Operable Breast Cancer Patients

Purpose: To study the prognostic significance of elevated cytokeratin 19 (CK19) mRNA levels in the bone marrow (BM) of operable breast cancer patients.

Patients And Methods: From 1998 to 2000, BM was collected from 195 consecutive breast cancer patients immediately prior to surgery and from 34 healthy volunteers. The patients received surgical and adjuvant treatment according to national guidelines at the time. We analyzed the level of CK19 mRNA in the BM samples from patients and normal controls using a real-time RT-PCR assay. The associations with known prognostic factors and the impact of pathological CK19 mRNA levels on patients' prognosis were investigated.

Results: Using the 99 percentile of the normal control group as a cut-off, 24 (12%) of the 195 patients and 1 (3%) of the 34 volunteers were diagnosed as CK19 mRNA positive. There was no correlation between CK19 BM status and the clinicopathological factors tested. During a median follow-up of 72 months, 7 (29%) of the 24 CK19 mRNA BM positive patients experienced systemic relapse compared to 20 (12%) of the 171 in the CK19 mRNA negative group. The patients with CK19 mRNA-positive BM had significantly shorter systemic recurrence-free survival (P=0.01) and overall recurrence-free survival (P=0.005). Multivariate Cox regression showed CK19 mRNA BM status to be an independent predictor of relapse.

Conclusion: Detection of CK19 mRNA in the BM of breast cancer patients by real-time RT-PCR is an independent predictor of relapse-free survival in operable breast cancer patients.