Roles of Ki-67, p53, transforming growth factor-β and lysyl oxidase in the metastasis of lung cancer

Respirology. 2014 Oct;19(7):1034-9. doi: 10.1111/resp.12345. Epub 2014 Jul 3.

Abstract

Background and objective: Most lung cancer (LC) patients have metastatic disease at time of diagnosis, which influence the treatment regimen and is the most important prognostic factor. The main purpose of our study was to evaluate the relationship between cell proliferation (Ki-67 label index), p53, transforming growth factor-β (TGF-β) and lysyl oxidase (LOX), and the metastatic stages of different lung cancers. The secondary aim was to correlate these parameters with the standardized uptake value (SUVmax) of the primary lesion during positron emission tomography-computed tomography (PET-CT).

Methods: Eighty-five treatment-naive patients with LC were enrolled. All patients were examined with PET-CT. Ki-67, p53, TGF-β and LOX were evaluated histopathologically.

Results: Small cell lung cancer (SCLC) showed the most intense staining in all parameters. A well-differentiated adenocarcinoma (AC) demonstrated a more diffuse and intense staining than squamous cell carcinoma (SCC). There was no statistically significant relationship between the four parameters and metastases of SCLC and SCC. However, a significant relationship between TGF-β, LOX and metastatic AC was demonstrated with regards to diffusivity and intensity. p53 and Ki-67 did not show a significant relationship. No correlation between SCLC and SCC and SUVmax was found. However, in AC, the diffusivity and intensity of the LOX and p53 staining showed a statistically significant relationship to the SUVmax.

Conclusions: LOX and TGF-β may play roles in metastatic AC. LOX and TGF-β may become markers of metastatic disease and inhibition could be explored for treatment.

Keywords: Ki-67; TGF-β.; lung cancer; lysyl oxidase; p53.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Cohort Studies
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Ki-67 Antigen / metabolism*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Male
  • Multimodal Imaging
  • Positron-Emission Tomography
  • Protein-Lysine 6-Oxidase / metabolism*
  • Radiopharmaceuticals
  • Small Cell Lung Carcinoma / diagnosis
  • Small Cell Lung Carcinoma / metabolism
  • Small Cell Lung Carcinoma / secondary
  • Tomography, X-Ray Computed
  • Transforming Growth Factor beta / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Ki-67 Antigen
  • Radiopharmaceuticals
  • Transforming Growth Factor beta
  • Tumor Suppressor Protein p53
  • Fluorodeoxyglucose F18
  • Protein-Lysine 6-Oxidase