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.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: F
authors.initials: F
authors.lastname: Lonardo
authors.forename: V
authors.initials: V
authors.lastname: Rusch
authors.forename: J
authors.initials: J
authors.lastname: Langenfeld
authors.forename: E
authors.initials: E
authors.lastname: Dmitrovsky
authors.forename: D S
authors.initials: DS
authors.lastname: Klimstra
mesh_terms: D001982:Bronchial Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001984:Bronchial Neoplasms / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D019927:Cyclin E / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D016161:Genes, Retinoblastoma; D006801:Humans; D008679:Metaplasia; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D012189:Retrospective Studies
chemical_list: D019927:Cyclin E; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1