Lymph node micrometastases do not predict relapse in stage II colon cancer

Background: Over one third of patients with stage II colonic adenocarcinoma experience tumor recurrence. Because effective adjuvant therapy is now ava ilable, it is important to identify subsets of patients at higher risk for relapse who may benefit from early treatment. Immunohistochemistry has been used to detect microscopic metastases in histologically uninvolved mesente ric lymph nodes, but the prognostic significance of minimal nodal involveme nt has not been established. Methods: Hematoxylin and eosin (H&E)-stained recuts of 900 mesenteric lymph nodes from 55 patients (range, 2-47; mean, 16.4 nodes per case) with resec ted pT3 or pT4, NO, MO (TNM stage II) colonic adenocarcinomas were re-exami ned for the presence of metastases and then stained immunohistochemically f or keratin using the AE1:AE3 antibody. Twenty-seven patients did not experi ence recurrence of tumor within 5 years following resection (no evidence of disease [NED]); 28 patients relapsed during the same time frame. Lymph nod es from 10 patients having colonic resections for nonneoplastic disorders a lso were stained as controls. Keratin-positive cells and cell clusters were quantified in the lymph nodes, and comparisons were made between patients with and without tumor relapse. Results: In the relapse group, four patients had positive nodes already ide ntified on the H&E-stained recuts and had to be excluded from further analy sis. Sixteen additional patients had keratin-positive cells; thus, 16 of 24 (67%) had micrometastases. In the NED group, one patient had a positive no de on H&E staining and 22 additional patients had keratin-positive cells, s o 22 of 26 (84%) patients had micrometastases. In the patients who had micr ometastases, there was a mean of 3.5 and 4.6 positive nodes in the relapse and NED groups, respectively, and a mean of 11.3 and 12.4 keratin-positive cells or clusters in the relapse and NED groups, respectively. No keratin-p ositive cells were found in the 1 to 21 (mean, 9.1) nodes per case studied in the control patients. Conclusions: Micrometastases to histologically uninvolved mesenteric lymph nodes commonly are detected in patients with pT3 or pT4 colonic adenocarcin omas on recuts stained immunohistochemically for keratin. Nodal micrometast ases detected by immunohistochemical staining are not useful for identifyin g stage II patients at higher risk for relapse.