Detection of CK-19 mRNA-positive cells in the peripheral blood of breast cancer patients with histologically and immunohistochemically negative axillary lymph nodes.
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.


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.
Stathopoulos
E N
EN
Department of Pathology, Medical School, University of Crete, University General Hospital of Heraklion, 71003 Heraklion, Crete, Greece. stath@med.uoc.gr
Sanidas
E
E
Kafousi
M
M
Mavroudis
D
D
Askoxylakis
J
J
Bozionelou
V
V
Perraki
M
M
Tsiftsis
D
D
Georgoulias
V
V
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000906:Antibodies; D001365:Axilla; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021701:Sentinel Lymph Node Biopsy
D000906:Antibodies; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D007633:Keratins