Relationship between stromal cells and tumor spread through air spaces in lung adenocarcinoma

The mechanism underlying tumor spread through air spaces (STAS) has not been well studied. We investigated the role of tumor stromal cells in the pathogenesis of STAS from a pathological perspective and evaluated the prognostic significance of tumor stromal cells and STAS in postoperative patients with lung adenocarcinoma.

We retrospectively analyzed 208 postsurgical patients with stage I-IIIA lung adenocarcinoma. The presence of STAS was evaluated by hematoxylin and eosin staining. The expression of α-smooth muscle actin (SMA)-positive cancer-associated fibroblasts (CAFs) and CD204-positive tumor-associated macrophages (TAMs) was analyzed by immunohistochemistry. A logistic regression model was applied to confirm the predictive factors of STAS. Survival analysis was performed to evaluate the effect of α-SMA-positive CAFs, CD204-positive TAMs, and STAS on prognosis. A nomogram was generated to evaluate the prognosis of postoperative patients.

Logistic regression suggested that the expression of α-SMA-positive CAFs (P < 0.001) and the number of CD204-positive TAMs (P < 0.001) were related to the presence of STAS. The multivariate Cox proportional hazards model suggested that STAS (P = 0.004), α-SMA-positive CAFs (P < 0.001), and CD204-positive TAMs (P < 0.001) were independent risk factors for prognosis. Harrell's c-indexes for overall and recurrence-free survival prediction based on nomograms were 0.84 (95% confidence interval 0.76-0.91) and 0.82 (95% confidence interval 0.76-0.89), respectively.

The presence of STAS was associated with high expression of α-SMA and CD204 in lung adenocarcinoma. Nomograms including STAS and stromal cells as variables are recommended as practical models to evaluate the prognosis of lung adenocarcinoma patients.