Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer

Br J Cancer. 1996 Feb;73(3):294-300. doi: 10.1038/bjc.1996.52.


Amplification of the CCDN1 gene encoding cyclin D1 was examined by Southern blotting and multiplex polymerase chain reaction (PCR) and occurred in 8 of 53 patients (15%) with primary resected non-small-cell lung cancer (NSCLC). These tumours and 17 additional tumours with a normal gene copy number showed overexpression of cyclin D1 (25/53, 47%), as assessed by immunostaining using a monoclonal antibody. In 22/25 cases, cyclin D1 was localised in the cytoplasm, but some (7/25) had simultaneous nuclear staining. This result is in marked contrast to that reported in breast, hepatocellular and colorectal carcinoma studies where immunostaining was invariably nuclear. Examination of a restriction fragment length polymorphic (RFLP) site within the 3'untranslated region of the cDNA following reverse transcriptase (RT)-PCR (29/53 informative cases) showed a strong association between cytoplasmic staining and imbalance in allele-specific message levels. Cyclin D1 overexpression was associated with a poorly differentiated histology (P = 0.04), less lymphocytic infiltration of the tumour (P = 0.02) and a reduction in local relapse rate (P = 0.01). The relative risk of local relapse was 9.1 in tumours without cyclin D1 overexpression (P = 0.01, Cox regression analysis). We conclude that genetic alteration of cyclin D1 is a key abnormality in lung carcinogenesis and may have diagnostic and prognostic importance in the treatment of resectable NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Base Sequence
  • Carcinoma, Small Cell / metabolism*
  • Cyclin D1
  • Cyclins / genetics*
  • DNA Primers / chemistry
  • Female
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Oncogene Proteins / genetics*
  • Prognosis
  • RNA, Messenger / genetics
  • Risk Factors


  • Cyclins
  • DNA Primers
  • Oncogene Proteins
  • RNA, Messenger
  • Cyclin D1