title: Synergistic effect of Bcl-2 and cyclin A2 on adverse recurrence-free survival in stage I non-small cell lung cancer.
abstract: BACKGROUND
  The prognostic significance of cyclin A2 overexpression in non-small cell lung cancer (NSCLC) is controversial.
  
  
  METHODS
  To understand the effect of cyclin A2 on recurrence in NSCLC, we retrospectively analyzed the expression of Bcl-2, cyclin A2, E-cadherin, Ki-67, and p53 using immunohistochemistry in 635 NSCLCs.
  
  
  RESULTS
  Overexpression of cyclin A2 was found in 466 (73%) of 635 NSCLCs, and recurrence occurred in 291 (46%) of 635 NSCLCs with a median follow-up of 5.4 years. The relationship between recurrence and cyclin A2 overexpression was not homogenous by pathologic stage (Breslow-Day test for homogeneity, P = 0.007). Overexpression of cyclin A2 was associated with poor recurrence-free survival (RFS) in 374 stage I NSCLCs (P = 0.02), and RFS was worse in patient with negative expression of Bcl-2 than those with positive expression of Bcl-2. Cox proportional hazard analysis showed that stage I NSCLC patients with overexpression of cyclin A2 and negative expression of Bcl-2 had poorer RFS (hazard ratio = 3.86, 95% confidence interval = 1.07-15.77; P = 0.03) than those with normal expression of cyclin A2 and Bcl-2, after adjusting for age, adjuvant radiotherapy, and histology. Neural network and generalized linear model including cyclin A2 and Bcl-2 showed best performance in the prediction of recurrence; error rates for neural network and generalized linear model were 15% and 12%, respectively.
  
  
  CONCLUSIONS
  Negative effect of cyclin A2 on RFS in stage I NSCLC was aggravated by negative expression of Bcl-2.
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea.
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Ko
authors.forename: Yujin
authors.initials: Y
authors.lastname: Kim
authors.forename: Eun Yoon
authors.initials: EY
authors.lastname: Cho
authors.forename: Jungho
authors.initials: J
authors.lastname: Han
authors.forename: Young Mog
authors.initials: YM
authors.lastname: Shim
authors.forename: Joobae
authors.initials: J
authors.lastname: Park
authors.forename: Duk-Hwan
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D056751:Cyclin A2 / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D056751:Cyclin A2; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1