Ian C. Talbot

The inflammatory response within Dukes’ B colorectal cancers: implications for progression of micrometastases and patient survival

OBJECTIVES:The aim of this study was to determine the relationship between the inflammatory response in primary colorectal carcinomas, patient outcome, and the fate of bone marrow micrometastases.METHODS:The populations studied were a) 155 consecutive patients with Dukes’ B colorectal cancer and follow-up for a mean of 5 yr, from the Mercy Hospital, Cork, and b) 260 consecutive patients with rectal carcinoma Dukes’ B and follow-up for >10 yr, from St. Marks Hospital, London. The primary tumor was assessed for the Jass and “Crohns-like” lymphoid reactions. In 36 consecutive patients, bone marrow aspirates were examined for micrometastases before and ≥6 months postoperatively.RESULTS:The relationship between prognosis and the inflammatory reactivity in the tumors was similar in both populations. In the Mercy group there were two deaths among 40 patients who had coexistent Jass and Crohns-like infiltrates. This contrasted with 25 deaths among 58 patients in whom both infiltrates were absent (p < 0.005). Results were intermediate in cases in which either type of inflammatory reaction was present alone. In the St. Marks patients similar prognostic differences were sustained for up to 10 yr. Bone marrow micrometastases were present in 12/36 patients preoperatively and in 14/36 postoperatively. Seven of 12 patients with preoperative micrometastases were negative postoperatively, indicating clearance of tumor cells. Nine of 24 who tested negative preoperatively had micrometastases postoperatively. The clearance and presence of postoperative micrometastases was related to the immunological responses in the primary tumor.CONCLUSIONS:These results demonstrate an association between the inflammatory reaction, prognosis, and clearance of micrometastases, indicating a systemic antitumor reaction that confers a survival advantage.

Association Between a High Number of Isolated Lymph Nodes in T1 to T4 N0M0 Colorectal Cancer and the Microsatellite Instability Phenotype

HYPOTHESIS Stage I or II colorectal carcinomas with microsatellite instability (MSI) are characterized by more isolated lymph nodes in the resected specimen than their counterparts with microsatellite stability (MSS). DESIGN Prospective study. SETTING Academic research. PATIENTS Using a pentaplex polymerase chain reaction assay, MSI status was determined prospectively for 135 operative patients. MAIN OUTCOME MEASURES Mismatch repair defects were investigated by immunohistochemistry on tumors demonstrating MSI. RESULTS Among 82 stage I or II colorectal carcinomas, 11 had MSI, and 71 had MSS, with a mean (SD) number of 23.6 (3.1) and 13.7 (1.0) negative lymph nodes, respectively (P = .001). The mean number of lymph nodes for all resected stage I or II colorectal carcinomas analyzed at our hospital was 15. The prevalence of MSI among tumors with more than 15 lymph nodes in the specimen was 25% (9 of 36), and 82% (9 of 11) of MSI tumors belonged to this group. CONCLUSIONS A high number of isolated lymph nodes in stage I or II colorectal carcinomas was associated with the MSI phenotype. Good prognosis that is usually associated with tumors having a high number of uninvolved lymph nodes might reflect the high prevalence of MSI among these tumors. The number of examined lymph nodes as a quality criterion should be used with caution. For stage I or stage II colorectal carcinomas, restricting MSI phenotyping to tumors with more than the mean number of lymph nodes identifies almost all MSI tumors.