Tumor progression after curative resection of colorectal cancer is caused b
y tumor cell dissemination, currently undetected by standard clinical stagi
ng techniques. The detection of disseminated tumor cells could help to iden
tify a patient subgroup at risk for disease relapse who could benefit from
adjuvant therapy. In addition, the significance of lymphogenic compared wit
h hematogenic colorectal cancer cell dissemination is unknown. However, thi
s knowledge would strongly influence the development of future therapeutic
regimes. The purpose of this study was to determine the extent of colorecta
l cancer cell dissemination in lymph nodes compared with blood and bone mar
row. Using a CK 20-reverse transcription (RT)-PCR assay, we examined 279 ly
mph nodes, blood, and bone marrow samples from 20 patients with colorectal
cancer. Of 16 patients (11 patients stage I, 5 patients stage II) with hist
opathologically tumor-free lymph nodes: 14 patients (10 patients stage I, 4
patients stage II) were found to have tumor cells in paracolonic lymph nod
es; 12 patients (8 patients stage I, 4 patients stage II) were found to hav
e tumor cells in the lymph nodes along the mesentery vessels; and, remarkab
ly, 6 patients (4 patients stage I, 2 patients stage II) were found to have
tumor cells in the apical lymph nodes. In contrast, tumor cells were detec
ted in only two blood and three bone marrow samples of these patients. Thus
, lymphogenic tumor cell dissemination is a very common and early event in
colorectal cancer, preceding hematogenic tumor cell dissemination. In addit
ion, our data strongly suggest that the detection of tumor cells in the api
cal lymph node by CK 20-RT-PCR has prognostic relevance. Our results underl
ine the therapeutic importance of meticulous lymph node dissection and demo
nstrate that the detection of lymphogenic or hematogenic tumor cell dissemi
nation by CK 20-RT-PCR will significantly improve current tumor staging pro
tocols.