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
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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.
Reprint requests to Hiroko Nogi, Department of Surgery, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.
Mansi JL, Berger U, Easton D, McDonnell T, Redding WH, Gazet J, Mckinna A, Powles T, Coombes RC: Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases.Br Med J 295: 1093–1097, 1987.CrossRef
Mansi JL, Easton D, Berger U, Gazet JC, Ford HT, Dearnaley D, Coombes RC: Bone marrow micrometastases in primary breast cancer: prognostic significance after 6 years’ follow-up.Eur J Cancer 27: 1552–1555, 1991.PubMed
Cote RJ, Rosen PP, Lesser ML, Old LJ, Osborne MP: Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases.Clin Oncol 9: 1794–1756, 1991.
Dearnaley DP, Ormerod MG, Sloane JP: Micrometastases in breast cancer: long-term follow-up of the first patient cohort.Eur J Cancer 27: 236–239, 1991.PubMed
Harbeck N, Untch M, Pache L, Eiermann W: Tumor cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up.Br J Cancer 69: 566–571, 1994.PubMed
Gerber B, Krause A, Muller H, Richter D, Reimer T, Makovitzky J, Herrning C, Jeschke U, Kundt G, Friese K: Simultaneous immunohistochemical detection of tumor cells in lymph nodes and bone marrow aspirates in breast cancer and its correlation with other prognostic factors.Clin Oncol 19: 960–971, 2001.
Roth MS, Antin JH, Bingham El, Ginsberg D: Detection of Philadelphia chromosome positive cells detected by the polymerase chain reaction following bone marrow transplant for chronic myelogenous leukemia.Blood 74: 882–885, 1989.PubMed
Moss TJ, Sanders DJ: Detection of neuroblastoma cells in blood.Clin Oncol 8: 736–740, 1990.
Jauch KW, Heiss MM, Gruetzner U, Funke I, Pantel K, Babic R, Eissner HJ, Roethmuller G, Schilberg FW: Prognostic significance of bone marrow micrometastases in patients with gastric cancer.Clin Oncol 14: 1810–1817, 1996.
Osborne MP, Asina S, Wong GY, Old LJ, Cote RJ: Immunofluorescent monoclonal antibody detection of breast cancer in bone marrow: sensitivity in a model system.Cancer Res 49: 2510–2513, 1989.PubMed
Eliss G, Ferguson M, Yamanaka E, Livingston RB, Gown AM: Monoclonal antibodies for detection of occult carcinoma cells in bone marrow of breast cancer patients.Cancer 63: 2509–2514, 1989.CrossRef
Datta YH, Adams PT, Drobyski WR, Either SP, Terry VH, Roth MS: Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction.Clin Oncol 12: 475–482, 1994.
Schoenfeld A, Kruger KH, Gomm J, Gazet JC, Sacks N, Bender HG, Luqmani Y, Coombes RC: The detection of micrometastases in the peripheral blood and bone marrow of patients with breast cancer using immunohistochemistry and reverse transcriptase polymerase chain reaction for keratin 19.Eur J Cancer 33: 854–861, 1997.PubMedCrossRef
Zippelius A, Kufer P, Honold G, Kollermann MW, Oberneder R, Schlimok G, Reithmuller G, Pantel K: Limitations of reverse-transcriptase polymerase chain reaction analyses for detection of micrometastatic epithelial cancer cells in bone marrow.Clin Oncol 15: 2701–2708, 1997.
Memeto T, Vana J, Bedwana RN: Management and survival of female breast cancer.Cancer 45: 2917–2924, 1980.CrossRef
Rosen PP, Saigo PE, Braun DW, Weathers E, DePalo A: Prediction of recurrence in stage I (T1N0M0) breast carcinoma.Cancer 193: 15–25, 1981.
Miura S: The prognostic significance of axillary node metastasis in breast cancer.Jpn J Breast Cancer 10: 452–459, 1995.
Redding WH, Coombes RC, Monaghan P, Clink HM, Imrie SF, Dearnaley DP, Ormerod MG, Sloane JP, Gazet JC, Powles TJ, Neville AM: Detection of micrometastases in patients with primary breast cancer.Lancet 2: 1271–1274, 1983.PubMed
Miyake Y, Fujiwara Y, Ohue M, Yamamoto H, Sugita Y, Tomita N, Sekimoto M, Shiozaki H, Monden M: Quantification of micrometastases in lymph nodes of colorectal cancer using real-time fluorescence polymerase chain reaction.Int J Oncol 16: 289–293, 2000.PubMed
Brugger W, Buhring HJ, Grunebach F, Vogel W, Muller R, Brummendorf TH, Ziegler BL, Brossat P, Scheding S, Kanz L: Expression of MUC-1 epitopes on normal bone marrow: implications for the detection of micrometastatic tumor cells.Clin Oncol 17: 1535–1544, 1999.
Traweek ST, Liu J, Rattifora H: Keratin gene expression in non-epithelial tissues: detection with polymerase chain reaction.Am J Pathol 142: 1111–1118, 1993.PubMed
- 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
Volume 10, Issue 1 , pp 74-81
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- Bone marrow
- Quantitative RT-PCR
- Keratin 19
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- Author Affiliations
- 1. Departments of Surgery and Environmental Medicine, Jikei University School of Medicine, Japan
- 2. Departments of Public Health and Environmental Medicine, Jikei University School of Medicine, Japan
- 3. Departments of Oncology, Institute of DNA Medicine, Jikei University School of Medicine, Japan
- 4. Departments of Molecular Genetics, Institute of DNA Medicine, Jikei University School of Medicine, Japan