Extensive micrometastases to lymph nodes as a marker for rapid recurrence of colorectal cancer: A study of lymphatic mapping

To provide a detailed assessment of micrometastases of colorectal cancer by anatomical mapping of regional lymph nodes (LNs), we analyzed 237 LNs from II patients with colorectal cancer by reverse transcription-PCR (RT-PCR) u sing carcinoembryonic antigen and cytokeratin 20 as genetic markers, All di ssected LNs were mapped anatomically and subjected to detection assays for micrometastases, Immunohistochemical analysis was also performed using anti -pancytokeratin antibody AE1/AE3 to confirm the existence of occult cancer cells. By histological analysis, 20 of 237 LNs contained metastatic cells, and they were ah positive by both immunohistochemistry and RT-PCR, Of the 2 17 histologically negative LNs, 14 (6.5%) harbored micrometastases by immun ohistochemistry, and 57 (26.2%) were positive for at least one of the two g enetic markers. Lymphatic mappings of all patients showed that micrometasta ses were distributed not only at the pericolic LNs but often at distant LNs , Clinical follow-up study showed that two patients developed recurrence wi thin 1 year after surgery, and both of them had RT-PCR-positive micrometast ases in not less than 70% of LNs examined. Moreover, both patients had freq uent micrometastases at distant LNs, i,e,, those around the root or along t he inferior mesenteric artery, when compared with patients with no recurren ce. Our findings suggest that genetic diagnosis using the RT-PCR method may be clinically useful along with conventional pathological diagnosis, espec ially when micrometastases spread to distant LNs.