title: RB protein status and clinical correlation from 171 cell lines representing lung cancer, extrapulmonary small cell carcinoma, and mesothelioma.
abstract: We have studied RB protein expression in 171 cell lines derived from patients with small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), pulmonary carcinoid, mesothelioma, and extrapulmonary small cell cancer (EPSC) and have correlated this data with clinical outcome. We detected absent or aberrant RB protein expression in 66/75 SCLC, 12/80 NSCLC, 1/6 carcinoid, 0/5 mesothelioma, and 4/5 EPSC samples. In addition, we observed integration of human papilloma virus (HPV) DNA in the single EPSC cell line that retained wildtype RB protein. We did not detect integration of HPV, SV40 or adenoviral DNA in other tumor samples with wildtype RB status. We also noted a stable, hypophosphorylated mutant RB in 12 SCLC and 3 NSCLC samples which might have been falsely interpreted as wildtype by current immunohistochemical techniques. Analysis of the matched clinical data showed no associations between RB status and age, sex, extent of disease, performance status, smoking history, and previous treatment. In addition, retrospective analyses showed no consistent correlation of RB protein expression with either best clinical response, overall survival, or in vitro chemotherapeutic drug sensitivity. The stable expression of RB after gene transfection into RB(-) SCLC cells, however, resulted in a trend toward increased in vitro resistance to etoposide, cisplatin and doxorubicin.
authors.affiliation: National Cancer Institute-Navy Oncology Branch, National Cancer Institute, Bethesda, Maryland 20889.
authors.forename: E
authors.initials: E
authors.lastname: Shimizu
authors.forename: A
authors.initials: A
authors.lastname: Coxon
authors.forename: G A
authors.initials: GA
authors.lastname: Otterson
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: R A
authors.initials: RA
authors.lastname: Kratzke
authors.forename: Y W
authors.initials: YW
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Fedorko
authors.forename: H
authors.initials: H
authors.lastname: Oie
authors.forename: B E
authors.initials: BE
authors.lastname: Johnson
authors.forename: J L
authors.initials: JL
authors.lastname: Mulshine
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000401:mortality; D018288:Carcinoma, Small Cell / Q000737:chemistry* / Q000401:mortality; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000401:mortality; D008297:Male; D008654:Mesothelioma / Q000737:chemistry* / Q000401:mortality; D008875:Middle Aged; D016160:Retinoblastoma Protein / Q000032:analysis*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D016160:Retinoblastoma Protein