Fibroblast Activation Protein-α Expressing Fibroblasts Promote Lymph Node Metastasis Esophageal Squamous Cell Carcinoma

Background and Objectives: Esophageal squamous cell carcinoma (ESCC) remains one of the most common malignancies in China and has a high metastasis rate and poor prognosis. Fibroblast activation protein-alpha (FAP-alpha) is a serine peptidase the expression of which in cancer-associated fibroblasts has been associated with a higher risk of metastases and poor survival. This study aimed to analyze the correlation of FAP-alpha expression with the lymph node metastasis and prognostic significance in ESCC. Methods: FAP-alpha expression was examined in 121 resected ESCC specimens and 10 adjacent normal tissue using immunohistochemistry. FAP-alpha expression was scored in the stromal fibroblasts adjacent to neoplastic nests. A chi-square test was used to analyze the correlation between FAP-alpha expression in tumors stromal and lymph node metastasis of ESCC. The association between FAP-alpha expression and prognosis was evaluated using univariable and multivariable statistical modeling. Results: FAP-alpha expression was absent in the benign controls. FAP-alpha expression was evident in the stromal 37% (45/121) of ESCC. Expression of FAP-alpha level is significantly associated with lymph node metastasis (p=0.023), but it is not correlated to age, gender, and tumor location in ESCC patients. Stromal FAP-alpha expression was significantly associated with poor survival in univariable (HR 2.009; 95% CI 1.259-3.205; p=0.003) and multivariable analysis (HR 1.833; 95% CI 1.144-2.937; p=0.012). Conclusion: FAP-alpha may be an important regulator in lymph node metastasis of ESCC and may provide a novel therapeutic target in ESCC.