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

2.50
Hdl Handle:
http://hdl.handle.net/10541/95647
Title:
Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer.
Authors:
Betticher, Daniel C; Heighway, Jim; Hasleton, Philip S; Altermatt, H J; Ryder, W David J; Cerny, T; Thatcher, Nick
Abstract:
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.
Affiliation:
CRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.
Citation:
Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer. 1996, 73 (3):294-300 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Feb-1996
URI:
http://hdl.handle.net/10541/95647
PubMed ID:
8562333
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBetticher, Daniel Cen
dc.contributor.authorHeighway, Jimen
dc.contributor.authorHasleton, Philip Sen
dc.contributor.authorAltermatt, H Jen
dc.contributor.authorRyder, W David Jen
dc.contributor.authorCerny, Ten
dc.contributor.authorThatcher, Nicken
dc.date.accessioned2010-04-06T10:28:44Z-
dc.date.available2010-04-06T10:28:44Z-
dc.date.issued1996-02-
dc.identifier.citationPrognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer. 1996, 73 (3):294-300 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid8562333-
dc.identifier.urihttp://hdl.handle.net/10541/95647-
dc.description.abstractAmplification 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.en
dc.language.isoenen
dc.subjectLung Canceren
dc.subject.meshAged-
dc.subject.meshAlleles-
dc.subject.meshBase Sequence-
dc.subject.meshCarcinoma, Small Cell-
dc.subject.meshCyclin D1-
dc.subject.meshCyclins-
dc.subject.meshDNA Primers-
dc.subject.meshFemale-
dc.subject.meshGene Amplification-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshHumans-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshOncogene Proteins-
dc.subject.meshPrognosis-
dc.subject.meshRNA, Messenger-
dc.subject.meshRisk Factors-
dc.titlePrognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren

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