Analysis of NSCLC tumour heterogeneity, proliferative and 18F-FDG PET indices reveals Ki67 prognostic role in adenocarcinomas

Histopathology. 2016 Apr;68(5):746-51. doi: 10.1111/his.12808. Epub 2015 Oct 23.

Abstract

Aims: The role of tumour metabolic and proliferative indices in predicting non-small-cell lung cancer (NSCLC) patients' prognosis is unclear. We correlated fluorine 18 ((18) F)-fluorodeoxyglucose (FDG)-positron emission tomography (PET) value and Ki67 index to patients' survival, taking into account tumour heterogeneity, disease characteristics and genetic aberrations.

Methods and results: A series of 383 NSCLCs was arranged into tissue microarrays and Ki67 staining was analysed by immunohistochemistry. The maximum standardized uptake (SUV(MAX) ) value detected by (18) F-FDG-PET analysis was calculated over a region of interest. Large-cell and squamous cell carcinomas had higher proliferative and metabolic activities than adenocarcinomas, and the two measures were correlated significantly. The hot-spot Ki67 value was correlated with patients' survival and the cut-off to discriminate patients in the survival risk groups was 20%. Ki67 hot-spot values were greater in anaplastic lymphoma kinase (ALK) rearranged tumours. Adenocarcinomas showed the highest intratumour heterogeneity in proliferative activity and the hot-spot Ki67 value predicted only the prognosis of patients in this group. Although tumour metabolic activity was not associated with patients' prognosis, a SUV(MAX) > 2 was related to nodal metastases, tumour size and grade.

Conclusions: Our results highlight how tumour heterogeneity influences evaluation of prognostic biomarkers. Our data support Ki67 evaluation to estimate NSCLC patients' prognosis, particularly for adenocarcinoma.

Keywords: Ki67; PET; adenocarcinoma; lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aged
  • Carcinoma, Large Cell
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Ki-67 Antigen / metabolism*
  • Lung Neoplasms
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Prognosis
  • Radiopharmaceuticals

Substances

  • Ki-67 Antigen
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18