Overexpression of cyclins D1 and E is frequent in bronchial preneoplasia and precedes squamous cell carcinoma development Journal Article

  


Authors: Lonardo, F.; Rusch, V.; Langenfeld, J.; Dmitrovsky, E.; Klimstra, D. S.
Article Title: Overexpression of cyclins D1 and E is frequent in bronchial preneoplasia and precedes squamous cell carcinoma development
Abstract: Increased protein expression of the G1 cyclins D1 and E is reported in invasive non-small cell lung carcinoma. However, during transformation of the bronchial epithelium, overexpression of these species occurs, and their relationship to aberrant expression of p53 and retinoblastoma (Rb) has not been described previously. To determine the expression of these cell cycle regulators during the development of invasive squamous cell carcinoma (SCC) of the lung, the immunohistochemical expression patterns in normal bronchial epithelium (n = 36), squamous metaplasia (SM; n = 28), and epithelial atypia (n = 34) were compared with that in low-grade dysplasia (LGD; n = 17), high- grade bronchial dysplasia (HGD; n = 30), and SCC (n = 36). Monoclonal anti- p53 Pab1801, polyclonal anti-cyclin D1 DCS6, monoclonal anti-cyclin E HE12, and monoclonal anti-Rb OP-66 antibodies were used. Cyclin D1 was not expressed in normal bronchial epithelium but was detected in 7% of SMs, 15% of atypias; 18% of LGDs, 47% of HGDs, and 42% of SCCs. Cyclin E was not detected in normal epithelium (n = 24), SM (n = 16), or LGD (n = 12), but it was found in 9% of atypias (2 of 22), 33% of HGDs (7 of 21), and 54% of SCCs (13 of 24). p53 was not expressed in normal epithelium, SM, and LGD, but it was overexpressed in 6% of atypias, 53% of HGDs, and 61% of SCCs. Abnormal Rb expression was found only in 2 of 36 cases of SCC. A total of 91% of HGDs and 92% of SCCs exhibited overexpression of at least one of the p53, cyclin D1, or cyclin E species. However, no link was observed between overexpression of p53 and the overexpressed G1 cyclins in preneoplastic lesions. Overexpression of cyclin D1, cyclin E, and p53 occurs frequently and independently in pulmonary SCC and is detected in lesions before the development of invasive carcinoma. In contrast, altered Rb expression is a late and infrequent event in squamous cell carcinogenesis.
Keywords: immunohistochemistry; controlled study; protein expression; metaplasia; retrospective studies; human cell; squamous cell carcinoma; carcinoma, squamous cell; cell proliferation; cell division; gene overexpression; neoplasm proteins; protein p53; carcinogenesis; cell transformation, neoplastic; monoclonal antibody; gene expression regulation; gene expression regulation, neoplastic; staining; epithelial cells; down regulation; invasive carcinoma; neoplasm invasiveness; cyclin d1; retinoblastoma protein; protein determination; cyclin e; bronchus tumor; bronchial neoplasms; precancerous conditions; bronchial diseases; genes, retinoblastoma; humans; human; priority journal; article
Journal Title: Cancer Research
Volume: 59
Issue: 10
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 1999-05-15
Start Page: 2470
End Page: 2476
Language: English
PUBMED: 10344760
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0033563132&partnerID=40&md5=4ec105faa6771aabc048d37aaf5b2920
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus
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MSK Authors
  1. Valerie W Rusch
    865 Rusch
  2. David S Klimstra
    978 Klimstra
  3. Fulvio B Lonardo
    23 Lonardo
  4. Ethan Dmitrovsky
    98 Dmitrovsky
  5. John E. Langenfeld
    14 Langenfeld
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