Detailed examination of lymph nodes improves prognostication in colorectal cancer

Up to 30% of stage II patients with curatively resected colorectal cancer (CRC) will develop disease recurrence. We evaluated whether examination of lymph nodes by multilevel sectioning and immunohistochemical staining can improve prognostication. Lymph nodes (n = 780) from 36 CRC patients who had developed disease recurrence (cases) and 72 patients who showed no recurrence of disease for at least 5 years (controls) were analyzed. Sections of 4 levels at 200-mu m interval were immunohistochemically stained for cytokeratin expression. The first level was analyzed by conventional and automated microscopy, and the 3 following levels were analyzed by automated microscopy for the presence of tumor cells. Overall, cases showed more micrometastases (3 patients) than controls (1 patient). Analysis of a second level led to the additional detection of 1 patient with micrometastases (case) and 1 patient with macrometastasis (case). Examining more levels only led to additional isolated tumor cells, which were equally divided between cases and controls. Likewise, automated microscopy resulted only in detection of additional isolated tumor cells when compared with conventional microscopy. In multivariate analysis, micrometastases [odds ratio (OR) 26.3, 95% confidence interval (CI) 1.9-364.8, p = 0.015], T4 stage (OR 4.8, 95% CI 1.4-16.7, p = 0.013) and number of lymph nodes (OR 0.9, 95% CI 0.8-1.0, p = 0.028) were independent predictors for disease recurrence. Lymph node analysis of 2 levels and immunohistochemical staining add to the detection of macrometastases and micrometastases in CRC. Micrometastases were found to be an independent predictor of disease recurrence. Isolated tumor cells were of no prognostic significance.</p

Sialyl Lewis X Expression and Lymphatic Microvessel Density in Primary Tumors of Node-negative Colorectal Cancer Patients Predict Disease Recurrence

Up to 30% of curatively resected colorectal cancer patients with tumor-negative lymph nodes, show disease recurrence. We assessed whether these high-risk patients can be identified by examining primary tumors for the following blood and lymphatic vasculature markers: A) sialyl Lewis X (sLeX), vascular endothelial growth factor (VEGF)-C and VEGF-D expression; B) blood and lymphatic microvessel density (BMVD/LMVD); and C) the presence of blood and lymphatic vessel invasion. Thirty-six cases (disease recurrence within 5 years) and 72 controls (no disease recurrence for at least 5 years) were selected in a case-control design. Tumor sections were stained by antibodies CSLEX1 (sLeX), anti-VEGF-C, anti-VEGF-D, anti-CD31 (BMVD) or D2–40 (LMVD) to determine the parameters as mentioned above. A multivariate analysis showed sLeX expression and high LMVD (odds ratio 5.1, 95% confidence interval 1.3–20.0 and odds ratio 3.1, 95% confidence interval 1.0–10.0, respectively) to be independent factors predicting disease recurrence. Expression of sLeX correlated with liver metastases (P = 0.015). A high LMVD was related to regional intra-abdominal or intrapelvic metastases in lymph nodes and distant metastases other than in the liver and lungs such as peritoneum, bones, brain and adrenal glands (P = 0.004). A high BMVD in the invasive front correlated with lung metastases (P = 0.018). We show that high-risk node-negative colorectal cancer patients can be identified by primary tumor assessment for sLeX expression and LMVD. Our results are consistent with the notion that both lymphatic and hematogenous metastasis play a role in colorectal cancer