title: Detection of micrometastatic tumor cells in pN0 lymph nodes of patients with completely resected nonsmall cell lung cancer: impact on recurrence and Survival.
abstract: OBJECTIVE
  To detect occult micrometastatic tumor cells in pN0 lymph nodes of nonsmall cell lung cancer (NSCLC) by a combination of cytokeratin and p53 immunohistochemistry staining, and to evaluate the relation between the micrometastasis in pN0 lymph nodes and the prognosis of patients with completely resected stage 1 NSCLC.
  
  
  BACKGROUND
  The average 5-year survival rate for patients with completely resected stage 1 NSCLC is only about 70%; thus, about 30% of these patients have recurrent disease. This suggests that occult micrometastasis may exist at the time of surgery; the rate is clearly underestimated by current clinical staging examinations and conventional histopathologic methods.
  
  
  METHODS
  A total of 474 hilar and mediastinal lymph nodes were removed during surgery from 49 patients with completely resected stage 1 NSCLC. The lymph nodes analyzed for micrometastasis using immunohistochemical staining with the biclonal anticytokeratin antibody, AE1/AE3. Of these 474 lymph nodes from 49 patients, 263 lymph nodes from 25 patients, whose primary tumors were positive for the p53 protein, were subjected to immunohistochemical staining with the monoclonal anti-p53 protein antibody DO-1.
  
  
  RESULTS
  Cells positive for cytokeratin and p53 protein were found in 35 (7.4%) of 474 and 20 (7.6%) of 263 lymph nodes, respectively; 17 (34.7%) of 49 patients had cytokeratin-positive cells and 10 (40.0%) of 25 patients had p53-positive cells in their pN0 lymph nodes. By a combination of cytokeratin and p53 protein immunohistochemical staining, micrometastatic tumor cells were identified in pN0 lymph nodes in 22 (44.9%) of 49 patients. The patients with lymph node micrometastasis identified by a combination of cytokeratin and p53 protein immunohistochemical staining had a poorer prognosis than those without micrometastasis on both univariate and multivariate analyses (overall survival, P =.0003 and 0.013, respectively).
  
  
  CONCLUSIONS
  The detection of lymph nodal micrometastasis by cytokeratin and p53 protein immunohistochemical staining will be helpful to predict the recurrence and prognosis of patients with completely resected stage 1 NSCLC.
authors.affiliation: Department of Surgery II, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Chun-Dong
authors.initials: CD
authors.lastname: Gu
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Osaki
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Oyama
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inoue
authors.forename: Mantaro
authors.initials: M
authors.lastname: Kodate
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Dobashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oka
authors.forename: Kosei
authors.initials: K
authors.lastname: Yasumoto
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000601:surgery*; D016009:Chi-Square Distribution; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008175:Lung Neoplasms / Q000401:mortality / Q000601:surgery*; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D016019:Survival Analysis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D016159:Tumor Suppressor Protein p53; D007633:Keratins