Fig. 2
Heterogeneity of topoisomerase 1 expression in colorectal cancer specimens at each depth. A Representative topoisomerase 1 (TOPO1) immunohistochemistry in colorectal cancer (CRC) in the mucosal surface area (depth 1); 98.5% of CRC cells were positive for TOPO1 (134/136 cells) in this case. Bar, 50 μm. B Representative topoisomerase 1 (TOPO1) immunohistochemistry in colorectal cancer (CRC) in the TB area (depth 5); No cells were positive for TOPO1 in this case. Bar, 50 μm. C Heterogeneity of the positive ratio of TOPO1 in CRC cells at each depth; Boxplots showed that the TOPO1-positive ratios at depth 1, 2, 3, 4, and 5 were 80.3 ± 12.7%, 60.0 ± 28.8%, 30.4 ± 33.4%, 27.5 ± 32.6%, and 5.7 ± 6.7%, respectively (n = 20, *P < 0.05, **P < 0.01). The statistically significant difference was observed between depth 1 and 3, 1 and 4, 1 and 5, 2 and 4, and 2 and 5. D Representative heatmap of TOPO1-IHC; The red to yellow colored area indicates a higher density of TOPO1-positive cells in the mucosal area (depth 1–3). The green to blue colored area indicates a lower density of TOPO1-positive cells in the invasive front without TB (depth 4) and TB area (depth 5). E Correlation between the positive ratio of TOPO1 in CRC cells and the depth of CRC specimens; the TOPO1-positive ratio was negatively correlated with depth by scatter plot analysis (n = 20, rs = − 0.6700, P < 0.01)