Prognostic impact of cancer-associated stromal cells in patients with stage I lung adenocarcinoma

Chest. 2012 Jul;142(1):151-158. doi: 10.1378/chest.11-2458.


Background: The tumor microenvironment, of which cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are the major cellular components, plays an important role in tumor progression. This study evaluated the significance of podoplanin-positive CAFs and CD204-positive TAMs, which may reflect tumor-promoting CAFs and TAMs, as risk factors for recurrence in patients with stage I lung adenocarcinoma.

Methods: The expression of podoplanin in CAFs and CD204 in TAMs was analyzed by immunohistochemistry in 304 patients with stage I lung adenocarcinoma who underwent surgical resection between September 1992 and July 2004. The recurrence-free proportion (RFP) was estimated using the Kaplan-Meier method.

Results: The presence of podoplanin-positive CAFs and the higher number of CD204-positive TAMs were associated with a lower 5-year RFP (P < .001 and P = .001, respectively). Podoplanin-positive CAFs were an independently statistically significant risk factor for recurrence with the highest hazard ratio (3.474, P = .029, by multivariate Cox proportional hazards model). According to subgroup analyses combining podoplanin-positive CAFs and other independent risk factors (visceral pleural invasion and intratumoral vascular invasion), the 5-year RFPs were 95.6%, 92.3%, 80.5%, and 30.3% (P = .294, P = .067, and P < .001) for patients with zero, one, two, or three risk factors, respectively.

Conclusions: Podoplanin-positive CAFs were the most powerful independent risk factor for recurrence in patients with stage I lung adenocarcinoma. Podoplanin-positive CAFs may be useful for identifying patients with a high risk of recurrence who might benefit from adjuvant chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / surgery
  • Aged
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Scavenger Receptors, Class A / metabolism
  • Stromal Cells / metabolism
  • Stromal Cells / pathology*


  • MSR1 protein, human
  • Membrane Glycoproteins
  • PDPN protein, human
  • Scavenger Receptors, Class A