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

Ann Oncol. 2005 Feb;16(2):240-6. doi: 10.1093/annonc/mdi043.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Antibodies
  • Axilla
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Immunohistochemistry
  • Keratins / analysis*
  • Lymphatic Metastasis*
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating*
  • Prognosis
  • RNA, Messenger / analysis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sentinel Lymph Node Biopsy


  • Antibodies
  • Biomarkers, Tumor
  • RNA, Messenger
  • Keratins