© 2005 European Society for Medical Oncology
Original article |
Detection of CK-19 mRNA-positive cells in the peripheral blood of breast cancer patients with histologically and immunohistochemically negative axillary lymph nodes
Departments of 1 Pathology, 2 Surgical Oncology and 3 Medical Oncology, University General Hospital of Heraklion, Crete, Greece
* Correspondence to: Dr E. N. Stathopoulos, Department of Pathology, Medical School, University of Crete, PO Box 2208, 71003 Heraklion, Crete, Greece. Tel: +30-2810-394692; Fax: +30-2810-394694; Email: stath{at}med.uoc.gr
Background: To investigate the incidence of direct hematogenous spread of cancer cells in patients with early-stage breast cancer by studying the presence of occult tumor cytokeratin-19 (CK-19) mRNA+ cells in the peripheral blood in relation to the status of sentinel (SLNs) and (ALNs) axillary lymph nodes.
Patients and methods: SLNs and ALNs from 111 patients with operable stage I–II breast adenocarcinoma were evaluated for the presence of tumor cells by hematoxylin–eosin (H&E) staining and, if negative, by immunohistochemistry (IHC) using an anti-CK-19 antibody. Peripheral blood was also analyzed for the presence of CK-19 mRNA+ cells by nested RT–PCR, before the initiation of adjuvant treatment and in CK-19 mRNA+ patients following the completion of adjuvant chemotherapy and hormonal treatment.
Results: After both H&E staining and IHC analysis, 29 (26%) patients were ALN negative (N0). In 78 (70%) patients H&E staining and in four (3.6%) IHC analysis revealed tumors cells, and these patients were considered as ALN positive (N+). Peripheral blood CK-19 mRNA+ cells were detected in nine (31%) out of 29 N0 and in 31 (38%) out of 82 N + patients (P=0.5) before any adjuvant treatment. Adjuvant chemotherapy and hormone treatment resulted in the disappearance of the CK-19 mRNA+ cells in all N0 patients and in 15 out of 31 N + patients. After a median follow-up of 40 months, all the N0 CK-19 mRNA+ patients were relapse-free whereas four (13%) N + CK-19 mRNA+ patients had relapsed.
Conclusions: Direct hematogenous dissemination of occult tumor cells may occur in a substantial proportion of patients with early-stage breast cancer. The prognostic implication of the detection of these cells requires long follow-up periods and further studies.
Key words: breast cancer, CK-19 mRNA+ cells, hematogenous spread, micrometastatic disease, occult tumor cells, sentinel lymph nodes
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