Prognostic value of genomic alterations in minimal residual cancer cells purified from the blood of breast cancer patients.
The prognostic value of disseminated tumour cells derived from 353 breast cancer patients was evaluated. Disseminated tumour cells were purified from blood using a newly established method and nucleic acids were subsequently isolated. We investigated genomic imbalances (GI) such as mutation, amplification and loss of heterozygosity of 13 tumour suppressor genes and 2 proto-oncogenes using DNA from isolated minimal residual cancer cells. Significant correlations were found between genomic alterations of the DCC - and c-erbB-2 genes in disseminated breast cancer cells and actuarial relapse-free survival. Furthermore, increasing numbers of genomic imbalances measured in disseminated tumour cells were significantly associated with worse prognosis of recurrent disease. Logistic regression and Cox multivariate analysis led to the identification of genomic imbalances as an independent prognostic factor. Determination of disseminated tumour cells by genotyping of oncogenes and tumour suppressor genes seems not only to be a useful adjunct in follow up of carcinoma patients but provides also valuable additional individualized prognostic and predictive information in breast cancer patients beyond the TNM system.
Austrup
F
F
Institut für Molekulare NanoTechnologie, Berghäuser Str. 295, Recklinghausen, 45659, Germany.
Uciechowski
P
P
Eder
C
C
Böckmann
B
B
Suchy
B
B
Driesel
G
G
Jäckel
S
S
Kusiak
I
I
Grill
H J
HJ
Giesing
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics; D000075389:DCC Receptor; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual / Q000097:blood / Q000235:genetics* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011956:Receptors, Cell Surface; D016160:Retinoblastoma Protein / Q000235:genetics; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; D004273:DNA, Neoplasm; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C501909:DCC protein, human