Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer.
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.
Betticher
D C
DC
CRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.
Heighway
J
J
Hasleton
P S
PS
Altermatt
H J
HJ
Ryder
W D
WD
Cerny
T
T
Thatcher
N
N
D000368:Aged; D000483:Alleles; D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012307:Risk Factors
D016213:Cyclins; D017931:DNA Primers; D015513:Oncogene Proteins; D012333:RNA, Messenger; D019938:Cyclin D1