Clinical significance of cancer-associated fibroblasts and their correlation with microvessel and lymphatic vessel density in lung adenocarcinoma.

Background: To determine whether cancer-associated fibroblasts (CAFs) are associated with microvessel density (MVD) and lymphatic vessel density (LVD) in lung adenocarcinoma (ADC) or are not prognostic.

Methods: Ninety-three lung adenocarcinoma patients without adjuvant therapy between January 2010 and June 2011 were enrolled. CAFs, MVD, and LVD were identified by α-smooth muscle actin (α-SMA), CD34 and D2-40 staining via immunohistochemistry. Staining intensities were assessed and quantified. For statistics, Pearson's chi-square test, logistic regression, Kaplan-Meier, and log-rank tests were applied. In addition, the Cox proportional hazards model was used for multifactor analysis to predict survival.

Results: CAFs abundance in lung adenocarcinoma is associated with higher MVD and LVD. In addition, a correlation was demonstrated between MVD and LVD (P < 0.05). CAFs, MVD, and LVD are significantly correlating with age, tumor size, differentiation grade, clinical stage, and lymph node metastasis (P < 0.05), but not influenced by gender, tumor location, and smoking history. Three-year overall survival in the CAFs-poor group is 64.5%, which is significant higher than that in the CAFs-rich cohort (41.9%). Further, we found that age, clinical stage, α-SMA, CD34, D2-40 positivity, tumor size, differentiation grade, and lymph node metastasis significantly correlate with overall survival of patients with lung adenocarcinoma. However, sex, smoking history, and tumor location have no association with 3-year survival. The clinical stage is an independent prognostic factor in overall survival (P < 0.05).

Conclusions: The density of CAFs identified by α-SMA staining is associated with progression and metastasis of lung adenocarcinoma and affects the patient's disease outcome.