Shin Nari, Son Gyung Mo, Shin Dong-Hoon, Kwon Myeong-Sook, Park Byung-Soo, Kim Hyun-Sung, Ryu Dongryeol, Kang Chi-Dug
Department of Pathology, Hanyang University Hanmaeum Changwon Hospital, Changwon, Korea.
Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea.
Ann Coloproctol. 2019 Feb;35(1):36-46. doi: 10.3393/ac.2018.09.10. Epub 2019 Feb 28.
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).
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.
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.
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.
我们评估了癌症相关成纤维细胞（CAFs）和促结缔组织增生反应与结直肠癌（CRC）患者癌症侵袭性及长期预后的关系。
通过观察CRC组织瘤内基质和浸润前沿的胶原纤维结构及成纤维细胞的细胞形态，对成熟CAFs和促结缔组织增生进行组织学评估。使用淋巴浸润、血管浸润、神经周围浸润、肿瘤芽生和肿瘤生长模式评估癌细胞侵袭性。分析总生存期和全身复发情况。对CAF成熟度、促结缔组织增生反应和癌症侵袭性进行网络分析。
瘤内基质和浸润前沿成熟CAFs的比例分别为57.6%和60.3%。与未成熟CAFs相比，浸润前沿成熟CAFs中表皮生长因子受体（EGFR）的过表达明显更高。随着瘤内基质中成熟成纤维细胞数量的增加，淋巴浸润增加。在成熟和未成熟基质样本中，几乎一半都观察到肿瘤芽生，且在浸润性肿瘤中更频繁发生。在网络分析中，发现了与EGFR过表达、CAF成熟度和导致肿瘤芽生的浸润性肿瘤生长模式相关联的连接良好的岛状结构。
CAFs的成熟度和促结缔组织增生反应与癌症侵袭相关。然而，CAFs的细胞形态学特征作为CRC患者的独立预后因素并不充分。
