Clinical significance of FAP-α on microvessel and lymphatic vessel density in lung squamous cell carcinoma

J Clin Pathol. 2018 Aug;71(8):721-728. doi: 10.1136/jclinpath-2017-204872. Epub 2018 Mar 20.

Abstract

Aims: We aimed to determine whether cancer-associated fibroblasts (CAFs) are associated with microvessel density (MVD) and lymphatic vessel density (LVD) in lung squamous cell carcinoma, as well as their clinical significance in predicting survival.

Methods: 122 patients were enrolled in the study. Samples were obtained on resection at the Department of Thoracic Surgery of the Qingdao Municipal Hospital between January 2011 and December 2014. Immunohistochemistry was used to determine vessel and lymphatic vessel density, and CAF abundance (fibroblast activation protein α (FAP-α) positivity). Statistical analyses were performed on 85 patients to test for correlation of CAF density and other clinicopathological variables with 3-year overall survival (OS) and disease-free survival (DFS).

Results: High stromal CAF abundance significantly correlated with increased MVD and LVD in lung squamous cell carcinoma (p<0.05). χ2 test revealed a significant association of CAF density with lymph node metastasis. Cox proportional hazards model showed that both higher CAF density and lymph node metastasis negatively correlate with survival. CAF density or lymph node status can be used as an independent prognostic factor to predict 3-year OS and DFS.

Conclusions: CAF density, identified by FAP-α staining pattern, should be considered as a novel biomarker for disease prognosis in patients with lung squamous cell carcinoma.

Keywords: lung cancer; metastasis; tumour markers.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Cancer-Associated Fibroblasts / chemistry*
  • Cancer-Associated Fibroblasts / pathology
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / surgery
  • Chi-Square Distribution
  • Disease-Free Survival
  • Endopeptidases
  • Female
  • Gelatinases / analysis*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / chemistry*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Lymphangiogenesis
  • Lymphatic Metastasis
  • Lymphatic Vessels / pathology*
  • Male
  • Membrane Proteins / analysis*
  • Microvessels / pathology*
  • Middle Aged
  • Multivariate Analysis
  • Neovascularization, Pathologic
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Serine Endopeptidases / analysis*
  • Time Factors

Substances

  • Biomarkers, Tumor
  • Membrane Proteins
  • Endopeptidases
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases