Breast Cancer

, 10:74

Detection of MUC1 and keratin 19 mRNAs in the bone marrow by quantitative RT-PCR predicts the risk of distant metastasis in breast cancer patients

  • Hiroko Nogi
  • Hiroshi Takeyama
  • Ken Uchida
  • Toshihiko Agata
  • Junko Horiguchi-Yamada
  • Hisashi Yamada
Original Article

DOI: 10.1007/BF02967629

Cite this article as:
Nogi, H., Takeyama, H., Uchida, K. et al. Breast Cancer (2003) 10: 74. doi:10.1007/BF02967629



Early detection of micrometastasis in bone marrow is critical for the prognosis of breast cancer patients. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) has been used to detect cancer cells in bone marrow, but its utility as a prognostic factor still remains obscure.

Materials and Methods

Bone marrow samples were aspirated from the anterosuperior iliac spine of 34 patients, immediately after their surgical procedures had been completed. Control samples were also obtained from 10 healthy adult volunteers. The total RNA was extracted from the mononuclear cells, and the expression levels of β-actin, MUC1 and keratin 19 mRNAs were studied by quantitative RT-PCR. Each mRNA level was scored according to the expression level. The sum of these expression scores was defined as the composite expression score, which was employed as the basis of the evaluation.


The mean follow-up period was 45 months. Nine patients developed distant metastases, and one developed local recurrence. The 4-year disease relapse rates were 75% (RR= 19.38; 95% CI: 1.94-193.20), 28% (RR=3.64; 95% CI: 0.43-31.18), and 8.3% for patients with composite expression scores of 5/6, 3/4 and 2, respectively. The difference among the three groups was statistically significant (log-rank test:p = 0.0029), and multivariate analysis also found the composite expression score to be an independent prognostic factor.


Breast cancer patients who show a high composite expression score in bone marrow have a significantly higher risk of recurrence.

Key words

Bone marrowMicrometastasesQuantitative RT-PCRMUC1Keratin 19



Reverse transcriptase-polymerase chain reaction


Estrogen receptor


Progesterone receptor

Copyright information

© The Japanese Breast Cancer Society 2003

Authors and Affiliations

  • Hiroko Nogi
    • 1
  • Hiroshi Takeyama
    • 1
  • Ken Uchida
    • 1
  • Toshihiko Agata
    • 2
  • Junko Horiguchi-Yamada
    • 3
  • Hisashi Yamada
    • 4
  1. 1.Departments of Surgery and Environmental MedicineJikei University School of MedicineJapan
  2. 2.Departments of Public Health and Environmental MedicineJikei University School of MedicineJapan
  3. 3.Departments of Oncology, Institute of DNA MedicineJikei University School of MedicineJapan
  4. 4.Departments of Molecular Genetics, Institute of DNA MedicineJikei University School of MedicineJapan