Prognostic implications of molecular and immunohistochemical profiles of the Rb and p53 cell cycle regulatory pathways in primary non-small cell lung carcinoma.

Hdl Handle:
http://hdl.handle.net/10147/208932
Title:
Prognostic implications of molecular and immunohistochemical profiles of the Rb and p53 cell cycle regulatory pathways in primary non-small cell lung carcinoma.
Authors:
Burke, Louise; Flieder, Douglas B; Guinee, Donald G; Brambilla, Elizabeth; Freedman, Andrew N; Bennett, William P; Jones, Raymond T; Borkowski, Andrew; Caporaso, Neil A; Fleming, Marian; Trastek, Victor; Pairolero, Peter; Tazelaar, Henry; Midthun, David; Jett, James R; Liotta, Lance A; Travis, William D; Harris, Curtis C
Affiliation:
Department of Pathology, Cork University Hospital, Cork, Ireland.
Citation:
Clin Cancer Res. 2005 Jan 1;11(1):232-41.
Journal:
Clinical cancer research : an official journal of the American Association for, Cancer Research
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/208932
PubMed ID:
15671551
Abstract:
PURPOSE: Many studies have highlighted the aberrant expression and prognostic significance of individual proteins in either the Rb (particularly cyclin D1, p16INK4A, and pRb) or the p53 (p53 and p21Waf1) pathways in non-small cell lung cancer. We hypothesize that cumulative abnormalities within each and between these pathways would have significant prognostic potential regarding survival. EXPERIMENTAL DESIGN: Our study population consisted of 106 consecutive surgically resected cases of predominantly early-stage non-small cell lung cancer from the National Cancer Institute-Mayo Clinic series, and assessment of proteins involved both immunohistochemical (cyclin D1, p21Waf1, pRb, p16INK4A, and p53) and mutational analysis (p53) in relationship to staging and survival. RESULTS: Cyclin D1 overexpression was noted in 48% of the tumors, p16INK4A negative in 53%, pRb negative in 17%, p53 immunopositive in 50%, p53 mutation frequency in 48%, and p21(Waf1) overexpression in 47%, none with prognostic significance. Cyclin D1 overexpression in pRb-negative tumors revealed a significantly worse prognosis with a mean survival of 2.3 years (P = 0.004). A simultaneous p53 mutation dramatically reduced the mean survival time to 0.9 years (P = 0.007). Cyclin D1 overexpression with either a p53 mutation or a p53 overexpression was also associated with a significantly poorer prognosis (P = 0.0033 and 0.0063, respectively). CONCLUSIONS: Some cumulative abnormalities in the Rb and p53 pathways (e.g., cyclin D1 overexpression and p53 mutations) significantly cooperate to predict a poor prognosis; however, the complexity of the cell cycle protein interaction in any given tumor warrants caution in interpreting survival results when specific protein abnormalities are taken in isolation.
Language:
eng
MeSH:
Aged; Carcinoma, Non-Small-Cell Lung/*metabolism/mortality/therapy; Cell Cycle; Cyclin D1/biosynthesis; DNA Mutational Analysis; Female; *Gene Expression Regulation, Neoplastic; Heterozygote; Humans; Immunohistochemistry/*methods; Lung Neoplasms/*metabolism/mortality/therapy; Male; Middle Aged; Mutation; Prognosis; Protein Binding; Retinoblastoma Protein/*biosynthesis/metabolism; Time Factors; Treatment Outcome; Tumor Suppressor Protein p53/*biosynthesis/genetics
ISSN:
1078-0432 (Print); 1078-0432 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorBurke, Louiseen_GB
dc.contributor.authorFlieder, Douglas Ben_GB
dc.contributor.authorGuinee, Donald Gen_GB
dc.contributor.authorBrambilla, Elizabethen_GB
dc.contributor.authorFreedman, Andrew Nen_GB
dc.contributor.authorBennett, William Pen_GB
dc.contributor.authorJones, Raymond Ten_GB
dc.contributor.authorBorkowski, Andrewen_GB
dc.contributor.authorCaporaso, Neil Aen_GB
dc.contributor.authorFleming, Marianen_GB
dc.contributor.authorTrastek, Victoren_GB
dc.contributor.authorPairolero, Peteren_GB
dc.contributor.authorTazelaar, Henryen_GB
dc.contributor.authorMidthun, Daviden_GB
dc.contributor.authorJett, James Ren_GB
dc.contributor.authorLiotta, Lance Aen_GB
dc.contributor.authorTravis, William Den_GB
dc.contributor.authorHarris, Curtis Cen_GB
dc.date.accessioned2012-02-03T15:07:46Z-
dc.date.available2012-02-03T15:07:46Z-
dc.date.issued2012-02-03T15:07:46Z-
dc.identifier.citationClin Cancer Res. 2005 Jan 1;11(1):232-41.en_GB
dc.identifier.issn1078-0432 (Print)en_GB
dc.identifier.issn1078-0432 (Linking)en_GB
dc.identifier.pmid15671551en_GB
dc.identifier.urihttp://hdl.handle.net/10147/208932-
dc.description.abstractPURPOSE: Many studies have highlighted the aberrant expression and prognostic significance of individual proteins in either the Rb (particularly cyclin D1, p16INK4A, and pRb) or the p53 (p53 and p21Waf1) pathways in non-small cell lung cancer. We hypothesize that cumulative abnormalities within each and between these pathways would have significant prognostic potential regarding survival. EXPERIMENTAL DESIGN: Our study population consisted of 106 consecutive surgically resected cases of predominantly early-stage non-small cell lung cancer from the National Cancer Institute-Mayo Clinic series, and assessment of proteins involved both immunohistochemical (cyclin D1, p21Waf1, pRb, p16INK4A, and p53) and mutational analysis (p53) in relationship to staging and survival. RESULTS: Cyclin D1 overexpression was noted in 48% of the tumors, p16INK4A negative in 53%, pRb negative in 17%, p53 immunopositive in 50%, p53 mutation frequency in 48%, and p21(Waf1) overexpression in 47%, none with prognostic significance. Cyclin D1 overexpression in pRb-negative tumors revealed a significantly worse prognosis with a mean survival of 2.3 years (P = 0.004). A simultaneous p53 mutation dramatically reduced the mean survival time to 0.9 years (P = 0.007). Cyclin D1 overexpression with either a p53 mutation or a p53 overexpression was also associated with a significantly poorer prognosis (P = 0.0033 and 0.0063, respectively). CONCLUSIONS: Some cumulative abnormalities in the Rb and p53 pathways (e.g., cyclin D1 overexpression and p53 mutations) significantly cooperate to predict a poor prognosis; however, the complexity of the cell cycle protein interaction in any given tumor warrants caution in interpreting survival results when specific protein abnormalities are taken in isolation.en_GB
dc.language.isoengen_GB
dc.subject.meshAgeden_GB
dc.subject.meshCarcinoma, Non-Small-Cell Lung/*metabolism/mortality/therapyen_GB
dc.subject.meshCell Cycleen_GB
dc.subject.meshCyclin D1/biosynthesisen_GB
dc.subject.meshDNA Mutational Analysisen_GB
dc.subject.meshFemaleen_GB
dc.subject.mesh*Gene Expression Regulation, Neoplasticen_GB
dc.subject.meshHeterozygoteen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunohistochemistry/*methodsen_GB
dc.subject.meshLung Neoplasms/*metabolism/mortality/therapyen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshMutationen_GB
dc.subject.meshPrognosisen_GB
dc.subject.meshProtein Bindingen_GB
dc.subject.meshRetinoblastoma Protein/*biosynthesis/metabolismen_GB
dc.subject.meshTime Factorsen_GB
dc.subject.meshTreatment Outcomeen_GB
dc.subject.meshTumor Suppressor Protein p53/*biosynthesis/geneticsen_GB
dc.titlePrognostic implications of molecular and immunohistochemical profiles of the Rb and p53 cell cycle regulatory pathways in primary non-small cell lung carcinoma.en_GB
dc.contributor.departmentDepartment of Pathology, Cork University Hospital, Cork, Ireland.en_GB
dc.identifier.journalClinical cancer research : an official journal of the American Association for, Cancer Researchen_GB
dc.description.provinceMunster-

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.