Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan; Department of Plastic Surgery, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan.
Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan.
Hum Pathol. 2018 Sep;79:1-8. doi: 10.1016/j.humpath.2018.03.006. Epub 2018 Mar 16.
Activated cancer-associated fibroblasts (CAFs) and fibroblasts that have undergone the epithelial-mesenchymal transition (EMT) in cancer stroma contribute to tumor progression and metastasis. However, no reports have investigated the CAF phenotype and its clinicopathological relevance in cutaneous malignant tumors, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM). Here, we investigated the CAF phenotype in cutaneous malignant tumors based on their histology and immunohistochemical expression of CAF-related markers, including adipocyte enhancer-binding protein 1 (AEBP1), podoplanin, platelet-derived growth factor receptor α (PDGFRα), PDGFRβ, fibroblast activating protein (FAP), CD10, S100A4, α-smooth muscle actin (α-SMA), and EMT-related markers (Zeb1, Slug, and Twist). In addition, we assessed the role of the CAF phenotype in cutaneous malignant cancers using hierarchical cluster analysis. Consequently, 3 subgroups were stratified based on the expression pattern of CAF- and EMT-related markers. Subgroup 1 was characterized by low expression of AEBP1, PDGFRα, PDGFRβ, FAP and Slug, whereas subgroup 2 was closely associated with high expression of PDGFRβ, S100A4 and Twist. In addition, high expression levels of podoplanin, PDGFRβ, CD10, S100A4, α-SMA, Zeb1, Slug and Twist were observed in subgroup 3. High expression of CD10 was commonly found in all 3 subgroups. These subgroups were correlated with histologic subtypes, that is, subgroup 1, MM; subgroup 2, BCC; and subgroup 3, SCC. We suggest that the expression pattern of CAF- and EMT-related proteins plays crucial roles in the progression of BCC, SCC, and MM.
活化的癌症相关成纤维细胞 (CAF) 和癌症基质中经历上皮-间充质转化 (EMT) 的成纤维细胞有助于肿瘤的进展和转移。然而，目前还没有报道研究 CAF 表型及其在皮肤恶性肿瘤中的临床病理相关性，包括基底细胞癌 (BCC)、鳞状细胞癌 (SCC) 和恶性黑色素瘤 (MM)。在这里，我们根据组织学和 CAF 相关标志物的免疫组织化学表达，研究了皮肤恶性肿瘤中的 CAF 表型，包括脂肪细胞增强结合蛋白 1 (AEBP1)、 podoplanin、血小板衍生生长因子受体α (PDGFRα)、PDGFRβ、成纤维细胞激活蛋白 (FAP)、CD10、S100A4、α-平滑肌肌动蛋白 (α-SMA) 和 EMT 相关标志物 (Zeb1、Slug 和 Twist)。此外，我们还使用层次聚类分析评估了 CAF 表型在皮肤恶性肿瘤中的作用。结果，根据 CAF 和 EMT 相关标志物的表达模式，将 3 个亚组分层。亚组 1 的特征是 AEBP1、PDGFRα、PDGFRβ、FAP 和 Slug 表达水平低，而亚组 2 与 PDGFRβ、S100A4 和 Twist 表达水平高密切相关。此外，在亚组 3 中还观察到 podoplanin、PDGFRβ、CD10、S100A4、α-SMA、Zeb1、Slug 和 Twist 的高表达水平。CD10 的高表达在所有 3 个亚组中均很常见。这些亚组与组织学亚型相关，即亚组 1，MM；亚组 2，BCC；亚组 3，SCC。我们认为，CAF 和 EMT 相关蛋白的表达模式在 BCC、SCC 和 MM 的进展中起着关键作用。
