Dept. Oral Pathology, Oral Medicine and Oral Radiology, School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel; Institute of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Dept. Oral Pathology, Oral Medicine and Oral Radiology, School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel.
Acta Histochem. 2019 Nov;121(8):151446. doi: 10.1016/j.acthis.2019.151446. Epub 2019 Oct 8.
To examine different immunophenotypes of cancer-associated fibroblasts (CAFs) in tongue squamous cell carcinoma (TSCC) and to investigate how they related to clinical outcomes.
Serial sections from 54 cases of TSCC were immunohistochemically stained with α-smooth muscle actin (αSMA, CAF marker) to determine CAF density, and double-immunostained with αSMA combined with CD80 and CD86 (myeloid/monocytic-derived cell markers), Nanog (mesenchymal stem cell marker) and CD133 (hematopoietic/endothelial stem cell marker). Density of cells co-expressing these marker combinations was semi-quantitatively assessed in 5 randomly selected high power fields within the tumor area and scored as 1 - one-to-five stained cells in each field, 2 - more than 5 stained cells in each field; any finding less than score 1, was allocated a score of 0.
There were 26 CAF-poor, 16 CAF-rich and 12 CAF-intermediated cases. CD86αSMA cells were the most frequent (80.4%) followed by CD80αSMA (72%) and NanogαSMA cells (56%). The CD133αSMA phenotype was found only in association with blood vessels. High density of αSMA CAFs was associated with disease recurrence and poor survival (p < 0.05). Increased density of CD86αSMA cells was significantly associated with CAF-rich tumors and with poor survival (p < 0.05).
In TSCC, CAFs demonstrate heterogeneous and overlapping phenotypes with the myeloid/monocytic type being the most frequent and having an impact on the clinical outcomes. Further studies are needed in order to further characterize CAF phenotypes in carcinomas of various oral sites, as this may open new frontiers for personalized medicine.
研究舌鳞状细胞癌（TSCC）中不同的癌相关成纤维细胞（CAF）免疫表型，并探讨其与临床结局的关系。
对 54 例 TSCC 患者的连续切片进行α-平滑肌肌动蛋白（αSMA，CAF 标志物）免疫组织化学染色，以确定 CAF 密度，并进行αSMA 与 CD80 和 CD86（髓系/单核细胞来源细胞标志物）、Nanog（间充质干细胞标志物）和 CD133（造血/内皮干细胞标志物）的双重免疫染色。在肿瘤区域的 5 个随机高倍视野中，对这些标志物组合共同表达的细胞密度进行半定量评估，并将其评分分为 1-每个视野中 1-5 个染色细胞，2-每个视野中多于 5 个染色细胞；任何评分低于 1 的发现均分配为 0 分。
有 26 例 CAF 稀少、16 例 CAF 丰富和 12 例 CAF 中等病例。CD86αSMA 细胞最为常见（80.4%），其次是 CD80αSMA（72%）和 NanogαSMA 细胞（56%）。CD133αSMA 表型仅与血管有关。αSMA CAF 的高密度与疾病复发和生存不良相关（p<0.05）。CD86αSMA 细胞密度增加与 CAF 丰富的肿瘤和生存不良显著相关（p<0.05）。
在 TSCC 中，CAF 表现出异质性和重叠的表型，其中髓系/单核细胞类型最为常见，并对临床结局产生影响。需要进一步研究以进一步描述各种口腔部位癌的 CAF 表型，这可能为个性化医疗开辟新的前沿。
