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.

Cancer-associated fibroblasts of colorectal cancer: Translational prospects in liquid biopsy and targeted therapy

“…A recent report has shown the association of multiple CAF markers, namely α-SMA, collagen I, and platelet-derived growth factor receptor-beta (PDGFR-β), which are widely distributed in the stroma, with high venous invasion in advanced CRC (Nishishita et al, 2018). This supports a previous observation of the correlation of α-SMA positive and desmin negative myofibroblasts in advanced CRC with malignancy potential (Takatsuna et al, 2016). On the contrary, the expression of podoplanin in CAFs indicates a favorable prognosis of CRC (Choi et al, 2013), although other reports have shown podoplanin expression as a marker for an unfavorable prognosis (Kitano et al, 2010;Schoppmann et al, 2013).…”

Expression of cancer-associated fibroblast markers in advanced colorectal cancer

“…High levels of α-SMA subtraction (P=0.002), collagen I (P=0.040), and PDGFR-β (P=0.040) expression areas tended to be associated with high venous invasion. α-SMA positive and desmin negative myofibroblasts in the advanced colorectal cancer is associated with malignant potential in previous study ( 16 , 17 ). Serum levels of Collagen I degradation telopeptide are correlated with staging and poor disease-free survival of colorectal patients ( 19 ).…”

“…Previous reports were accomplished about each CAF ( 13 , 16 – 19 ), but did not provided the information about the comparison of each CAF. We captured immunohistochemical staining images, and adjusted phases in each case by using Adobe Photoshop software (Adobe ® Photoshop ® CC 2014 ® ; USA) for image registration, and compared the different antibodies in the same field.…”

Epithelial to mesenchymal transition influences fibroblast phenotype in colorectal cancer by altering miR‐200 levels in extracellular vesicles

“…This is especially intriguing in CRC, where there is an excess of local TGF-β in the majority of tumours (Calon et al, 2012). The histological organisation of CAFs and cancer cells provides certain clues, with the co-localisation of myofibroblasts and invasive carcinoma cells reported in various solid tumours (Kawashiri et al, 2009;Öhlund et al, 2017;Takatsuna et al, 2016). In CRC, the most lethal CMS4 subtype produces a stroma rich in α-SMA-positive myofibroblasts (Becht et al, 2016;Guinney et al, 2015).…”