Cyclin D1 overexpression in non-small cell lung carcinoma: correlation with Ki67 labelling index and poor cytoplasmic differentiation

J Pathol. 1996 Dec;180(4):395-9. doi: 10.1002/(SICI)1096-9896(199612)180:4<395::AID-PATH688>3.0.CO;2-C.


Cyclin D1 is part of the molecular system regulating the cell cycle G1 to S transition point. Its overexpression, a common finding in carcinomas of the breast, oesophagus, and head and neck, has also been demonstrated in a high percentage of non-small cell lung carcinomas (NSCLCs). The role of cyclin D1 in NSCLC has been studied by correlating its immunoreactivity with the Ki67 labelling index in paraffin-embedded, autoclaved surgical samples of 56 NSCLC cases. In addition, flow cytometric determination of ploidy and cell cycle status was carried out on 172 fresh tumour samples from the same cases. Twenty-four (42.8 per cent) NSCLCs showed positive cyclin D1 immunostaining, a finding which showed no relationship to ploidy pattern, cell cycle phase, histological subtype, or lymph node metastasis, but was significantly associated with the Ki67 labelling index (P = 0.03) and with poor cytoplasmic differentiation (P = 0.01). Cyclin D1-positive nuclei were abundant in poorly differentiated zones and absent in the best differentiated areas, particularly in heavily keratinized fields. These data indicate that in NSCLC, cyclin D1 overexpression is not only associated with a high cell proliferation rate, but also seems to play a role in the process of tumour differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Cyclin D1
  • Cyclins / metabolism*
  • Cytoplasm / pathology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunoenzyme Techniques
  • Ki-67 Antigen / metabolism*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Oncogene Proteins / metabolism*


  • Cyclins
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Oncogene Proteins
  • Cyclin D1