Myofibroblast distribution is associated with invasive growth types of colorectal cancer

Abstract

Both the invasive growth types of colorectal cancer (CRC) and the number of myofibroblasts have been associated with histopathological factors such as lymph node and liver metastasis, and local recurrence. However, there are few studies, that have assessed the association between invasive growth type and myofibroblast distribution in CRC. We aimed to evaluate the relationship between the clinicopathological factors of CRC and two invasive growth types, the expanding and infiltrating types. We categorized 150 cases of pT3 CRC into the expanding and infiltrating types and measured the myofibroblast density of three histological layers: the submucosa (SM), the muscularis propria (MP) and the subserosa (SS). We compared these two invasive growth types and analyzed the relationship between clinicopathological factors and myofibroblast density. Myofibroblast density was significantly higher in the infiltrating type than that in the expanding type (P<0.05). In the lymph node metastasis-positive group of the infiltrating type, myofibroblast density in MP was significantly higher than that in the lymph node metastasis-negative group (P<0.001). In the infiltrating type, the group with the higher level of lymphatic invasion had a significantly higher density of myofibroblasts in the MP than the group with the lower level of lymphatic invasion (P<0.01). These results suggest that myofibroblasts participate more in the infiltrating type compared with the expanding type of CRC. It would appear that myofibroblasts present in the MP play an important role in the malignant potential of the infiltrating type compared to the expanding type.

Figure 1.

Expanding and infiltrating types of colorectal cancer, which invade through the mucosa to the subserosa. (A) The expanding type was recognized as the overall expansion growth type of adenocarcinoma and the invasive margin was clear. (B) The infiltrating type was recognized as the widespread streaming form of adenocarcinoma. Histology of the (C) expanding and the (D) infiltrating types around the tumor invasive lesion in the muscularis propria layer. M, mucosa; SM, submucosa; MP, muscularis propria; SS, subserosa.

Figure 2.

Representations of the expanding type around the invasive lesion of the muscularis propria layer: (A) hematoxylin and eosin staining, (B) α-SMA, (C) desmin and (D) subtraction image (α-SMA-desmin). Representations of the infiltrating type around the invasive lesion of the muscularis propria layer: (E) hematoxylin and eosin staining, (F) α-SMA, (G) desmin and (H) subtraction image (α-SMA-desmin). The red square is a 1×1 mm² area, which measures the myofibroblast density (D and H).

Figure 3.

Mean myofibroblast density in each layer around the invasive lesion of colorectal cancer. In both the SM and the MP, there was a significant difference in myofibroblast density between the expanding and infiltrating types. Values are given as the mean ± SEM. *P<0.05, ***P<0.001 for the expanding vs. the infiltrating type. ns, not significant; SM, submucosa; MP, muscularis propria; SS, subserosa.

Figure 4.

Mean myofibroblast density of lymph node metastasis-negative and -positive groups in the (A) expanding and the (B) infiltrating types. There was a significant difference between the lymph node metastasis-positive and metastasis-negative groups in regards to the myofibroblast density in the MP colorectal wall in the infiltrating type. Values are given as the mean ± SEM. ***P<0.001 the lymph node-negative group vs. the lymph node-positive group in regards to the infiltrating type. ns, not significant; SM, submucosa; MP, muscularis propria; SS, subserosa.

Figure 5.

Mean myofibroblast density in the low lymphatic vessel invasion and high lymphatic vessel invasion groups in the (A) expanding and the (B) infiltrating types. In the infiltrating type, there was a significant difference between the low and high lymphatic vessel invasion groups in regards to the myofibroblast density in the MP colorectal wall. Values are given as the mean ± SEM. **P<0.01 the low lymphatic vessel invasion group vs. the high lymphatic vessel invasion group in regards to the infiltrating type. ns, not significant; SM, submucosa; MP, muscularis propria; SS, subserosa.

Figure 6.

Mean myofibroblast density in the low venous invasion and high venous invasion groups in the (A) expanding and (B) infiltrating types. Values are given as the mean ± SEM. ns, not significant; SM, submucosa; MP, muscularis propria; SS, subserosa.