Figure 2

Gene expression profiling and intrahepatic expression of HBV antigens in HBV-associated HCC. (A) Heat map of 1,486 genes differentially expressed in different areas of livers containing HCC. These data were obtained from whole liver tissue. A denotes tumor center; B tumor periphery; C the perilesional non-tumorous area, outside the tumor margin; D a distance of 2-3 cm from the margin of the tumor; E the most distant non-tumorous area, the edge of the liver. Data from the center of the tumor (A) represent individual samples, whereas data from each of the remaining liver areas (from B to E) represent the average of multiple specimens obtained in the 4 directions (N, S, E, and W). Each cell represents the expression of a particular gene (rows) of a particular liver area (columns). The color in each cell reflects the level of expression of the corresponding gene in the corresponding area, relative to its mean level of expression in the entire set of 120 samples. Ratios were log2-transformed and row-wise standardized. Up-regulated genes are shown in shades of red, down-regulated genes in shades of green. (B) Frequency of positive hepatocytes for HBsAg immunostaining within and outside the tumor of 11 patients. Data are represented as mean SE. Liver samples for HBsAg staining from areas B and C were available in 8 patients (C). Sections representing different liver areas show a significant decrease in number of HBsAg-positive hepatocytes between the perilesional non-tumorous area (C) and the periphery of the tumor margin (B), which further decreased in the center of the tumor (A). HBsAg positivity was almost diffuse in the most distant non-tumorous area E, with a gradual decrease in area C, whereas scattered or isolated positive hepatocytes (Inset) were mostly found in areas B and A, respectively (Original magnification 20X).