Podoplanin expression in cancer‐associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma

Aims Podoplanin expression in cancer‐associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early‐stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p‐stage) IA lung adenocarcinoma as categorised by the 8th edition of the tumour–node–metastasis classification for lung cancer. Methods and results Immunohistochemical analyses using anti‐podoplanin antibody were performed on resected specimens from 158 patients with p‐stage IA lung adenocarcinoma. When more than 10% of cancer cells or CAFs showed immunoreactivity with podoplanin, the specimens were classified as podoplanin‐positive. Podoplanin‐positive status in cancer cells (n = 8) was not correlated with clinicopathological factors or with patient prognosis. Podoplanin‐positive status in CAFs (n = 41) was correlated significantly with poorer tumour differentiation (P < 0.001), the presence of lymphatic invasion (P < 0.001) and high‐grade (solid and/or micropapillary) components constituting ≥1% of the entire tumour (P < 0.001). The log‐rank test showed that podoplanin‐positive status in CAFs was associated significantly with shorter disease‐free survival (DFS) (P < 0.001) and disease‐specific survival (P = 0.015). In Cox's multivariate analysis, podoplanin‐positive status in CAFs had the most significant effect on shorter DFS [hazard ratio (HR) = 4.411, P = 0.004], followed by the presence of high‐grade components (HR = 3.581, P = 0.013). Conclusions Podoplanin expression in CAFs could be an independent predictor of increased risk of recurrence in patients with p‐stage IA lung adenocarcinoma.