Bone marrow cytokeratin 19 mRNA level is an independent predictor of relapse-free survival in operable breast cancer patients

• Published in: Breast cancer research and treatment Vol. 108; no. 2; pp. 251 - 258
• Main Authors: Farmen, Ragne K., Nordgård, Oddmund, Gilje, Bjørnar, Shammas, Fuad V., Kvaløy, Jan T., Oltedal, Satu, Heikkilä, Reino
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2008; Springer; Springer Nature B.V
• Subjects: Biological and medical sciences; Bone marrow; Bone Marrow - chemistry; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Cancer research; Cancer surgery; Cancer therapies; Chemotherapy, Adjuvant; Clinical outcomes; Clinical Trial; Clinical trials; Disease-Free Survival; Diseases of the osteoarticular system; Female; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Kaplan-Meier Estimate; Keratin-19 - analysis; Keratin-19 - genetics; Mammary gland diseases; Mastectomy; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Oncology; Predictive Value of Tests; Proportional Hazards Models; Proteins; Radiotherapy, Adjuvant; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment; RNA, Messenger - analysis; Survival analysis; Time Factors; Treatment Outcome; Tumors; Tumors of striated muscle and skeleton; Up-Regulation; Real-time RT-PCR; Bone marrow; Recurrence; Breast cancer; Cytokeratin 19; Micrometastases; Relapse free survival; Relapse; Breast disease; RNA-directed DNA polymerase; Diseases of the osteoarticular system; Tumoral marker; Micrometastases, Real-time RT-PCR, Cytokeratin 19; Messenger RNA; Micrometastasis; Reverse transcription polymerase chain reaction; Breast cancer, Bone marrow; Human; Enzyme; Transferases; Malignant tumor; Gene expression; Real time; Mammary gland diseases; Nucleotidyltransferases; Bone cancer; Molecular biology; Predictive factor; Cancer
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-007-9592-x

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.