title: Expression of HuR, COX-2, and survivin in lung cancers; cytoplasmic HuR stabilizes cyclooxygenase-2 in squamous cell carcinomas.
abstract: Hu antigen R (HuR) is a member of the human family of embryonic-lethal, abnormal vision-like proteins, which serves as an mRNA-binding protein. In the cytoplasm, HuR can stabilize the mRNA of cyclooxygenase-2 (COX-2), an enzyme that catalyses the synthesis of prostaglandins and is associated with promotion of carcinogenesis and tumor cell resistance to apoptosis. Intracellular (cytoplasmic and nuclear) localization of survivin has a prognostic significance as an apoptosis inhibitor and a regulator of cell division in tumors. Patients with 151 squamous cell carcinomas and 93 adenocarcinomas underwent lobectomy or pneumonectomy with hilar and mediastinal lymph node sampling. Paraffin-embedded tumor sections were retrieved for evaluation of nuclear and cytoplasmic staining of survivin and HuR, and cytoplasmic staining of COX-2. In squamous cell carcinomas, COX-2 expression was correlated with a difference of survivin (cytoplasmic-nuclear; P=0.004), cytoplasmic HuR (P=0.018), total HuR (cytoplasmic+nuclear; P=0.009), and difference of HuR (P=0.020). COX-2 was inversely correlated with nuclear survivin (P=0.006). In a univariate analysis by log-rank test, survival was associated with cytoplasmic survivin (adenocarcinoma, P<0.001; squamous cell carcinoma, P=0.005), difference of survivin (adenocarcinoma, P<0.001; squamous cell carcinoma, P=0.014), and COX-2 (squamous cell carcinoma, P=0.001). Survival was inversely associated with nuclear survivin (adenocarcinoma, P=0.006, squamous cell carcinoma, P=0.014). In a multivariate survival analysis, cytoplasmic survivin (adenocarcinoma, P=0.002; squamous cell carcinoma, P=0.015) and COX-2 (squamous cell carcinoma, P=0.020) were determined as independent prognostic factors. Cytoplasmic HuR expression is associated with COX-2 expression in squamous cell carcinomas. The expression of COX-2 in squamous cell carcinomas, and cytoplasmic survivin in adenocarcinomas and squamous cell carcinomas could be useful independent prognostic markers.
authors.affiliation: Department of Pathology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, South Korea. pathogen@medimail.co.kr
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Sung-Jig
authors.initials: SJ
authors.lastname: Lim
authors.forename: Youn Wha
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000201:enzymology / Q000276:immunology / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000201:enzymology / Q000276:immunology / Q000401:mortality / Q000601:surgery; D016009:Chi-Square Distribution; D051546:Cyclooxygenase 2 / Q000032:analysis*; D003593:Cytoplasm / Q000737:chemistry* / Q000201:enzymology / Q000276:immunology; D051959:ELAV Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000737:chemistry* / Q000201:enzymology / Q000276:immunology / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011013:Pneumonectomy; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D015996:Survival Rate; D000077022:Survivin; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051959:ELAV Proteins; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human