Ann Coloproctol.
2019 Feb;35(1):36-46. 10.3393/ac.2018.09.10.
Cancer-Associated Fibroblasts and Desmoplastic Reactions Related to Cancer Invasiveness in Patients With Colorectal Cancer
- Affiliations
-
- 1Department of Pathology, Hanyang University Hanmaeum Changwon Hospital, Changwon, Korea.
- 2Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea. skm1711@pusan.ac.kr
- 3Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan, Yangsan, Korea.
- 4Department of Pathology, Pusan National University Yangsan Hospital, Yangsan, Korea.
- 5Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Busan, Korea.
- 6Department of Biochemistry, Pusan National University School of Medicine, Busan, Korea.
- KMID: 2446792
- DOI: http://doi.org/10.3393/ac.2018.09.10
Abstract
- PURPOSE
We evaluated the relationship of cancer-associated fibroblasts (CAFs) and desmoplastic reactions with cancer invasiveness and long-term outcomes in patients with colorectal cancer (CRC).
METHODS
Histologic evaluation of mature CAFs and desmoplasia was performed by observing the collagen fiber structure and fibroblast cytomorphology in the intratumoral stroma and invasive front of CRC tissues. Cancer-cell invasiveness was evaluated using lymphatic invasion, vascular invasion, perineural invasion, tumor budding, and tumor growth patterns. Overall survival and systemic recurrence were analyzed. A network analysis was performed between CAF maturation, desmoplastic reaction, and cancer invasiveness.
RESULTS
The proportions of mature CAFs in the intratumoral stroma and the invasive front were 57.6% and 60.3%, respectively. Epidermal growth factor receptor (EGFR) overexpression was significantly higher in the mature CAFs in the invasive front as compared to immature CAFs. Lymphatic invasion increased as the number of mature fibroblasts in the intratumoral stroma increased. Tumor budding was observed in almost half of both mature and immature stroma samples and occurred more frequently in infiltrating tumors. On network analysis, well-connected islands were identified that was associated with EGFR overexpression, CAF maturation, and infiltrating tumor growth patterns leading to tumor budding.
CONCLUSION
The maturity of CAFs and desmoplastic reactions were associated with cancer invasion. However, the cytomorphologic characteristics of CAFs were insufficient as an independent prognostic factor for patients with CRC.
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