title: Prognostic role of p53 and Ki-67 immunohistochemical expression in patients with surgically resected lung adenocarcinoma: a retrospective study.
abstract: OBJECTIVE
  p53 mutations and the Ki-67 protein are frequently observed in various types of human cancer; the abnormal expression of p53 and Ki-67 in the tumor is associated with poor survival of lung cancer patients. We aimed to assess the prognostic role of immunohistochemical (IHC) expression of p53 and Ki-67 in lung adenocarcinoma tissue.
  
  
  METHODS
  Tumor samples from 136 patients who had undergone surgical resection for lung adenocarcinoma were retrospectively evaluated for p53 and Ki-67 expression by immunohistochemistry. Associations of clinical and pathologic variables with p53 and Ki-67 were determined using the χ(2) test. After excluding two patients (follow-up loss), 134 cases were evaluated for associations between p53, Ki-67, clinical and pathologic variables, and survival by using the Cox proportional hazards regression model and Kaplan-Meier method.
  
  
  RESULTS
  In the 136 patients, p53 was positive in 71.0% (93/131), and Ki-67 showed high in 49.2% (61/124). Unlike p53, Ki-67 was associated with male sex, smoking, and poor tumor differentiation (P=0.004, P=0.001 and P=0.006). Of these, poor tumor differentiation strongly was correlated with high level of Ki-67 expression (P=0.008). Neither p53 nor Ki-67 was associated with increased risk of death (P=0.318, P=0.053); however, age ≥60 years and lymph node involvement were significant predictors of death (P=0.039 and P=0.042). The log-rank test revealed a significant association between Ki-67 and lower survival in all patients (χ(2)=5637; P=0.018); however, the risk was limited to stage III cases (χ(2)=5.939; P=0.015). Unlike p53, patients with high level of Ki-67 expression showed lower 3-year actuarial survival than those without (log-rank test, χ(2)=4.936; P=0.026).
  
  
  CONCLUSIONS
  IHC expression of Ki-67 in lung adenocarcinoma tissue shows stronger association with poor tumor differentiation, and negatively affects patients' survival in advanced-stage lung cancer; however, the role of p53 on patient outcome needs further study.
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Cheol-Hong
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Hee Sung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Jeong-Hee
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Seung-Hun
authors.initials: SH
authors.lastname: Jang
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Yong-Bum
authors.initials: YB
authors.lastname: Park
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Myung Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Hyun
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Kun Il
authors.initials: KI
authors.lastname: Kim
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Hyoung Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Won Yong
authors.initials: WY
authors.lastname: Lee
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Eung-Joong
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Haeyoung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Shim
authors.affiliation: Departments of 1 Internal Medicine and Lung Research Institute, 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology and 4 Pathology, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Choi
keywords: Adenocarcinoma; Ki-67; lmmunohistochemistry; lung; p53; survival