Computerized nuclear morphometry of hepatocellular carcinoma and its relation to proliferative activity

Background and Objectives: Nuclear profiles have been reported as useful prognostic predictor in various cancers. Data from computerized morphometries are objective and can be quickly derived using conventional microscopic analysis. However, it remains to be shown what types of pathological and biological factors influence the nuclear features. The aim of this study was to evaluate the correlation between the morphological nuclear features and clinicopathological parameters in patients with hepatocellular carcinoma (HCC). Methods: Morphometric nuclear features (nuclear area, perimeter, and shape) were analyzed in 76 patients with hepatocellular carcinoma who underwent hepatectomy at our hospital. In each case, 300 cancer nuclei were analyzed randomly on routine hematoxylin&eosin-stained slides through the use of a computer-assisted image analysis system that allowed us to trace the nuclear profiles (magnification ×400) on a computer monitor. The morphometric data were compared with patient survival, clinico-pathologic status, and the proliferative activity of cancer cells. Results: The mean nuclear area of poorly differentiated carcinoma was significantly larger than that of moderately and well differentiated carcinoma (P = 0.0003). Significant correlation was detected between the nuclear area of cancer cells and proliferative activity associated with proliferating cell nuclear antigen labeling index (PCNA Ll) of cancer cells (r = 0.372, P = 0.0008). Moreover, blood vessel invasion of cancer cells or intrahepatic metastasis were more frequently detected in patients with large nuclear areas. Even though the nuclear area was not an independent prognostic factor in the multivariate analysis, the 5-year survival rate of the 35 patients who had tumors with large nuclear areas (>50 μm 2 . 25.9%) was significantly lower than that of the 36 patients who had tumors with small nuclear areas (<50 μm 2 , 63.3%, P = 0.001). Conclusions: The nuclear area of HCC correlates with cell differentiation and cell proliferative activity. Moreover, HCC with a large nuclear area has high potential for blood vessel invasion and intrahepatic metastasis. Thus, nuclear morphometry can be used as an useful morphological predictor for malignant potential in patients with HCC.