Tumor-associated gene expression in disseminated tumor cells correlates with disease progression and tumor stage in colorectal cancer.
BACKGROUND
A possible correlation of disease progression and tumor stage in colorectal cancer patients with tumor-associated gene expression in disseminated tumor cells (DTC) was evaluated. Detection of DTC and expression of tumor-associated genes might be of clinical value with respect to individual patient prognosis, monitoring of therapy and as a surrogate tumor staging parameter.


METHODS
In a multicenter study, a total of 196 peripheral blood samples were collected from 76 patients with tumor stage Dukes' A to D and analyzed using a DTC detection assay consisting of immunomagnetic selection and expression analysis of the tumor-associated genes CEA, EGFR and GA733-2. DTC detection rates were assessed prior to surgery and post surgery in patients with tumor stage Dukes' A, B and C, and compared with results in metastatic patients. CEA serum protein levels were determined and compared with DTC and CEA expression, respectively.


RESULTS
In a comparison analysis, EGFR and CEA expression was detected in 88% (p = 0.001) and 0% (p = 0.002) prior to surgery, in 66% (p = 0.001) and 20% (p = 0.002) post surgery, as well as in 15% (p < 0.0001) and 66% (p < 0.0001) of blood samples collected from metastatic patients, respectively. Expression of tumor-associated genes in DTC prior to surgery and in follow-up samples indicated an ongoing metastatic process. DTC detection rates in patients with Dukes' A (14%), Dukes' B (13%) and Dukes' C (40%) prior to surgery correlated statistically with the expected recurrence rate. There was no correlation between DTC expressing CEA and elevation of CEA serum protein levels.


CONCLUSIONS
EGFR and CEA gene expression correlated with disease progression and tumor stage. Detection of CEA expression in DTC might have a predictive value in colorectal cancer and may help to identify patients at a greater risk of relapse. DTC in peripheral blood collected prior to surgery as well as in follow-up samples have a prognostic clinical value.
Zieglschmid
Veit
V
AdnaGen AG, Ostpassage 7, D-30853 Langenhagen, Germany.
Hollmann
Christiane
C
Mannel
Jenny
J
Albert
Winfried
W
Jaeschke-Melli
Stefan
S
Eckstein
Birte
B
Hillemann
Tina
T
Greten
Tim F
TF
Gross
Eberhard
E
Böcher
Oliver
O
D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D018450:Disease Progression; D000071858:Epithelial Cell Adhesion Molecule; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D018189:Immunomagnetic Separation; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D066246:ErbB Receptors