title: Prognostic value of cytokeratin 19 fragment (CYFRA 21-1) and cytokeratin-positive cells in bone marrow samples of breast cancer patients.
abstract: The aim of this study was to investigate the relationship between the detection of micrometastatic cells by immunocytochemistry (ICC) with an anticytokeratin antibody and cytokeratin fragment (CYFRA 21-1) expression detected by an immunofluorescent assay in bone marrow of breast cancer patients. Micrometastatic CK+ cells were screened with a pancytokeratin antibody A45 B/B3 from bone marrow aspiration samples of 102 breast cancer patients (65 primary tumors, 10 local recurrences and 27 distant metastases). CYFRA 21-1 levels were assessed in bone marrow supernatant of these patients before collection of the mononucleated interface cells on a Ficoll-Hypaque density gradient and in 20 control patients. CYFRA 21-1 and CK+ cell detection by ICC were both correlated with clinical stage. CYFRA 21-1 was significantly elevated in patients with micrometastatic disease detected by ICC: 4.77 ng/mL (+/- 10.87 SD) versus 1.00 ng/mL (+/-1.36 SD) in patients with negative ICC (p=0.01). In univariate analysis, a CYFRA 21-1 value > or =1 ng/mL and the presence of CK+ cells were associated with a poorer survival for patients with stage I to III breast cancer (n=65). On multivariate analysis, only pathological nodal status and presence of CK+ cells in bone marrow were independent prognostic factors for overall survival. In conclusion, in this series CYFRA 21-1 was correlated with detection of CK+ cells by ICC in bone marrow, but cannot replace ICC. The presence of CK+ cells in bone marrow remains a strong independent prognostic factor in primary breast cancer.
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France. jean-yves.pierga@curie.net
authors.forename: J Y
authors.initials: JY
authors.lastname: Pierga
authors.forename: L
authors.initials: L
authors.lastname: Deneux
authors.forename: C
authors.initials: C
authors.lastname: Bonneton
authors.forename: A
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: C
authors.initials: C
authors.lastname: Nos
authors.forename: P
authors.initials: P
authors.lastname: Anract
authors.forename: H
authors.initials: H
authors.lastname: Magdelénat
authors.forename: P
authors.initials: P
authors.lastname: Pouillart
authors.forename: J P
authors.initials: JP
authors.lastname: Thiery
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053539:Keratin-19; D007633:Keratins / Q000096:biosynthesis*; D008856:Microscopy, Fluorescence; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D053539:Keratin-19; C102012:antigen CYFRA21.1; D007633:Keratins