Detection of Lymph Node Micrometastases in Colorectal Cancer

The presence of lymph node metastases is the single most important prognostic factor of colorectal cancer. However, almost one-third of patients considered metastases-free by routine histochemical analysis of lymph nodes subsequently develop tumour recurrence. More sensitive methods capable of detecting the small deposits of disseminated cancer cells forming micrometastases may provide a basis for powerful new prognostic markers and enhanced staging and treatment of patients with colorectal cancer. We present a review of recent methodology utilized to detect lymph node micrometastases in colorectal cancer, focusing on immunohistochemical staining and DNA- and RNA-based methods. Immunohistochemical staining is sensitive when single tissue sections are in focus, but is highly dependent upon the sectioning level, giving low overall sensitivity for whole lymph nodes unless the number of sections is high. Recent nucleic acid-based methods seem to have higher overall sensitivity, but have so far been used in a relatively limited number of studies, mostly without data on clinical outcome. Using multiple markers and sentinel node mapping can enhance the specificity and sensitivity of micrometastasis detection. Further investigation, however, is required before the most recent methodological developments can be incorporated in routine pathological examination.