基质成纤维细胞活化蛋白-α（FAP）作为喉高级别异型增生向鳞状细胞癌转变过程中侵袭的潜在辅助生物标志物
Stromal Fibroblast Activation Protein-α (FAP) as a Potential Adjunctive Biomarker of Invasion in the Transition From Laryngeal High-grade Dysplasia to Squamous Cell Carcinoma.
文献信息
| PMID | 42847181 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Francisco Javier Santaolalla |
| 作者单位 | Department of Otorhinolaringology, Basurto University Hospital (OSI-Bilbao Basurto), Bilbao, Bizkaia, Spain. |
| 期刊 | Applied immunohistochemistry & molecular morphology : AIMM |
| SCI 分区 | Q3 |
| IF | 1.4 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 咽喉科 |
中文摘要
背景： 鳞状上皮异型增生向浸润性喉鳞状细胞癌（LSCC）的转变是一个关键的生物学和诊断步骤，仅凭形态学难以界定。癌症相关成纤维细胞（CAFs）是恶性进展过程中基质活化的关键介质，而成纤维细胞活化蛋白（FAP）已成为肿瘤-基质相互作用和侵袭性的候选标志物。方法：我们评估了喉鳞状病变（n=83）中基质FAP的免疫组化表达，主要关注从高级别异型增生（HGD，n=23）到浸润性LSCC（n=57）这一具有诊断相关性的转变。该研究还包括3例低级别异型增生（LGD），以将分析扩展到非浸润性鳞状疾病的更早期阶段。结果：FAP表达在所有LGD中均缺失，在91.3%的HGD中缺失，而93%的LSCC显示基质FAP阳性（χ2检验，P=2.3×10-13）。受试者工作特征分析显示，其在识别浸润性疾病方面具有高诊断准确性，敏感性为93%，特异性为92.3%，曲线下面积为0.926（95%置信区间：0.856-0.997）。在一部分HPV相关癌中，还观察到局灶性上皮FAP表达。结论：这些发现表明，基质FAP表达可作为辅助生物标志物，支持常规组织病理学评估以识别基质侵袭，特别是在区分HGD与浸润性LSCC方面。
英文摘要
The transition from squamous epithelial dysplasia to invasive laryngeal squamous cell carcinoma (LSCC) is a critical biological and diagnostic step that is difficult to define using morphology alone. Cancer-associated fibroblasts (CAFs) are key mediators of stromal activation during malignant progression, and fibroblast activation protein (FAP) has emerged as a candidate marker of tumor-stroma interaction and invasiveness. We evaluated stromal FAP immunohistochemical expression in laryngeal squamous lesions (n=83), focusing primarily on the diagnostically relevant transition from high-grade dysplasia (HGD, n=23) to invasive LSCC (n=57). The study also included 3 low-grade dysplasias (LGD) to extend the analysis to an earlier stage of noninvasive squamous disease. FAP expression was absent in all LGDs and in 91.3% of HGDs, whereas 93% of LSCCs showed stromal FAP positivity (χ2 test, P=2.3×10-13). Receiver operating characteristic analysis demonstrated high diagnostic accuracy for identifying invasive disease, with a sensitivity of 93%, specificity of 92.3%, and an area under the curve of 0.926 (95% confidence interval: 0.856-0.997). In a subset of HPV-associated carcinomas, focal epithelial FAP expression was also observed. These findings suggest that stromal FAP expression may serve as an adjunctive biomarker to support conventional histopathologic assessment in the recognition of stromal invasion, particularly in the distinction between HGD and invasive LSCC.