The Association of Intratumoral Germinal Centers with early-stage non-small cell lung cancer

J Thorac Oncol. 2011 Oct;6(10):1687-90. doi: 10.1097/JTO.0b013e3182217bec.


Introduction: Lung cancers can display immune cell infiltration although the role of an adaptive immune response in disease pathogenesis is unknown. To investigate the possibility of a functional humoral response to the tumor, we surveyed histologic sections from non-small cell lung cancer (NSCLC) tumors for germinal centers (GCs) and assessed whether there was an association between the presence of GCs and tumor stage.

Methods: Tumor sections from 91 patients with all stages of NSCLC were examined by a pathologist blinded to clinical data. GCs were identified by hematoxylin and eosin staining patterns and confirmed by immunohistochemical staining for B-cell markers, BCL-6 and CD21. The distribution of GCs within the tumor or the tumor margin was recorded. Statistical analysis was performed to evaluate the association between stage and presence of GCs.

Results: Thirty-five percent of all tumors evaluated contained GCs, and sections evaluated by immunohistochemistry showed positive staining for both B-cell markers. GCs were seen both within the tumor and the tumor margin, consistent with an immune response to antigen stimulation. Patients with stage I NSCLC had a higher prevalence of intratumoral GCs than patients with stages II to IV (Cochran-Armitage Trend Test p = 0.02011). There was no association of stage with GCs in the tumor margin.

Conclusions: Intratumoral GCs are associated with early-stage NSCLC. Further characterization of intratumoral GCs may lead to new diagnostic and therapeutic strategies based on manipulation of the adaptive immune response.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adenocarcinoma, Bronchiolo-Alveolar / metabolism
  • Adenocarcinoma, Bronchiolo-Alveolar / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Large Cell / metabolism
  • Carcinoma, Large Cell / pathology*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Female
  • Follow-Up Studies
  • Germinal Center / pathology*
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism


  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2