Recruitment of podoplanin positive cancer-associated fibroblasts in metastatic lymph nodes predicts poor prognosis in pathological N2 stage III lung adenocarcinoma

Ann Surg Oncol. 2012 Nov;19(12):3953-62. doi: 10.1245/s10434-012-2421-4. Epub 2012 Jun 6.

Abstract

Background: Cancer-associated fibroblasts (CAFs) directly communicate with cancer cells and play important roles in cancer progression. Recent studies have reported that primary cancer tissue with podoplanin-expressing CAFs predicted a poorer outcome among stage I lung adenocarcinoma patients. However, whether podoplanin(+)-CAFs also can be recruited into metastatic lymph nodes and influence the prognosis remains unclear.

Methods: We selected 112 patients with pathological N2 stage III lung adenocarcinoma and examined the podoplanin expression of CAFs and their prognostic impact in primary and metastatic N2 lesions.

Results: Podoplanin(+)-CAFs were observed in 61 (54.5 %) primary sites and 44 (39.3 %) metastatic lymph nodes. Podoplanin(+)-CAFs were found at metastatic lymph nodes in 33 (54.1 %) primary podoplanin-positive and 11 (21.6 %) primary podoplanin-negative sites. These findings suggest a significant positive correlation in podoplanin expression in CAFs between pairs of primary and metastatic lesions (P < 0.001). The difference in the overall survival of patients with podoplanin-positive/negative CAFs in their primary lesion was not correlated (P = 0.927). In contrast, patients with podoplanin(+)-CAFs in metastatic lymph nodes had a shorter overall survival than those without podoplanin(+)-CAFs (P = 0.003). In multivariate analyses, podoplanin(+)-CAFs in metastatic lymph nodes were a significantly independent risk factor for a poor outcome (P = 0.007).

Conclusions: Our study indicated that podoplanin(+)-CAFs in metastatic lymph nodes was a significant prognostic factor for overall survival among pathological N2 stage III adenocarcinoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Large Cell / mortality
  • Carcinoma, Large Cell / secondary
  • Carcinoma, Large Cell / surgery
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / surgery
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Fluorescent Antibody Technique
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Lymph Nodes / pathology*
  • Lymph Nodes / surgery
  • Lymphatic Metastasis
  • Male
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / surgery
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Membrane Glycoproteins
  • PDPN protein, human