The ratio of cancer cells to stroma after induction therapy in the treatment of non-small cell lung cancer

J Cancer Res Clin Oncol. 2017 Feb;143(2):215-223. doi: 10.1007/s00432-016-2271-8. Epub 2016 Sep 17.

Abstract

Purpose: Induction therapy induces degenerative changes of various degrees in both cancerous and non-cancerous cells of non-small cell lung cancer (NSCLC). The effect of induction therapy on histological characteristics, in particular the ratio of residual cancer cells to non-cancerous components, is unknown.

Methods: Seventy-four NSCLC patients treated with induction therapy followed by surgery were enrolled. Residual cancer cells were identified using anti-pan-cytokeratin antibody (AE1/AE3). We analyzed and quantified the following three factors via digital image analysis; (1) the tumor area containing cancer cells and non-cancerous components (TA), (2) the total area of AE1/AE3 positive cancer cells (TACC), (3) the percentage of TACC to TA (%TACC). These factors were also analyzed in a matched control group (surgery alone, n = 80).

Results: The median TACC of the induction therapy group was significantly lower than that of the control group (p < 0.01). In addition, the median %TACC of the induction therapy group (5.9 %) was significantly lower than that of the control group (58.6 %) (p < 0.01). TACC had a strong positive correlation with TA in the control group (r = 0.93), but not in the induction therapy group. Conversely, TACC had a strong positive correlation with %TACC in the induction therapy group (r = 0.95), but not in the control group.

Conclusion: Unlike the control group, the smaller the total area of residual cancer cells, the higher residual tumor contained non-cancerous components in the induction group, which may be the characteristic histological feature of NSCLC after induction therapy.

Keywords: Cancer cell; Cancer stroma; Induction therapy; Non-small cell lung cancer.

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / therapy
  • Cell Count
  • Chemoradiotherapy, Adjuvant
  • Female
  • Humans
  • Induction Chemotherapy
  • Kaplan-Meier Estimate
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Stromal Cells / drug effects
  • Treatment Outcome
  • Tumor Burden