BACKGROUND: Approximately 25% of H&E node negative colon cancer (CC) patients recur. Detecting micrometastatic disease in these node negative patients may identify a high-risk group who would benefit from adjuvant treatment. This study was designed to assess the incidence of micrometastatic disease in H&E node negative CC patients by immunhistochemistry (IHC) and molecular staging, using sentinel lymph node (SLN) mapping as a tool to facilitate the identification of the regional lymph nodes most likely to harbor metastatic disease.
METHODS: (SLN) mapping using a 1cc peritumoral injection of lymphazurin blue was performed intraoperatively in 46 patients with resectable colon cancer. The sentinel node, a nearby nonsentinel node and a distant nonsentinel node were harvested after removal of the specimen. These nodes were then subjected to H&E analysis, IHC analysis with anti cytokeratin 20 (CK20), and RT-PCR analysis for CK20 expression.
RESULTS: The sentinel node was successfully identified in 39/46 cases (85%). One SLN was found in 19 cases, 2 SLN in 14 cases, 3 in 4 cases, 4 in 2 cases and 5 in one case (average of 1.6 SLN/patient). In 32/39 the SLN was negative for metastases by H&E. Preliminary data are reported on 18 of these patients with node negative disease (including the SLN) by H&E. A total of 33 SLN lymph nodes were examined. Of the 33 H&E negative nodes, 4 were found to have micrometastatic disease by IHC and 13 were found to have micrometastases by RT-PCR. On a patient basis, 3/18 (16%) were upstaged by IHC and 8/18 (44%) by RT-PCR. An additional 38 nonsentinel lymph nodes were analyzed. 0/38 were found to have micrometastases by IHC, however 8/38 were positive by RT-PCR leading to upstaging of an additional 3 patients and indicating a skip metastases rate of 3/18 (17%) by RT-PCR.
CONCLUSIONS: Both RT-PCR molecular staging and IHC analysis are more sensitive than H&E for detecting nodal micrometastasis. SLN mapping can facilitate identification of those lymph nodes which are likely to harbor micrometastatic disease, and then be subjected to more intense pathologic analysis that would not be practical for all harvested nodes. Long term follow up will determine whether these micrometastatic positive patients constitute a high-risk group for recurrent disease and therefore would benefit from adjuvant therapy.
