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.
BACKGROUND
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.


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 ofbeta-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.


RESULTS
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.


CONCLUSIONS
Breast cancer patients who show a high composite expression score in bone marrow have a significantly higher risk of recurrence.
Nogi
Hiroko
H
Department of Surgery, Jikei University School of Medicine, Japan. hirokong@db4.so-net.ne.jp
Takeyama
Hiroshi
H
Uchida
Ken
K
Agata
Toshihiko
T
Horiguchi-Yamada
Junko
J
Yamada
Hisashi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007633:Keratins / Q000032:analysis*; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008875:Middle Aged; D018396:Mucin-1 / Q000032:analysis*; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D016019:Survival Analysis
D018396:Mucin-1; D012333:RNA, Messenger; D007633:Keratins