Clinical significance of nuclear morphometry at the invasive front of T1 colorectal cancer and relation to expression of VEGF-A and VEGF-C.
OBJECTIVES: To better understand the metastatic potential of T1 colorectal cancer, we investigated variations in nuclear morphometry and expression of angiogenic factors in cancer cells at the invasive front. Sixty-five patients who had undergone curative resection were entered. METHODS: Nuclear shape factor, area, width, and proportion of cells with large nucleoli in all cells were determined in two high-power magnification areas at the invasive front of the tumor. We then performed the Ward method for cluster analysis. A dendrogram revealed that cases fell into two clusters: cluster A with high atypical nuclei and cluster B with low atypical nuclei. Expression of vascular endothelial growth factor-A (VEGF-A) and -C were evaluated immunohistochemically at the invasive front of the tumor. RESULTS: Nuclear atypia, and VEGF-C expression were associated significantly with lymph node metastasis by univariate analysis. Nuclear atypia was independently and significantly associated with lymph node metastasis by multivariate analysis. Whereas VEGF-A expression was associated with nuclear atypia, VEGF-C expression was not showed. Nuclear atypia, strong VEGF-A or -C expressions were not associated with the depth of invasion. CONCLUSION: Nuclear morphometry and expression of angiogenic factors at the invasive front are useful prognostic markers of lymph node metastasis, even cases with slight invasion.