title: Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small-cell lung cancer.
abstract: OBJECTIVE
  This prospective study was designed to evaluate the prognostic relevance and biologic characteristics of a minimal lymphatic tumor load in non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Frozen-tissue sections from 391 regional lymph nodes of 72 patients with completely resected NSCLCs, who were staged as free of metastases (pT1-3, pN0,M0,R0) by clinical tumor staging procedures and histopathologic examinations, were studied. For tumor-cell detection, we applied the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique with monoclonal antibody Ber-Ep4 against two glycoproteins of 34 and 49 kd present of the surface and cytoplasm of epithelial cells.
  
  
  RESULTS
  Individual Ber-Ep4-positive cells were detected in 11 of 72 (15.2%) cancer patients, while positive staining was consistently absent in all sections from control nodes of 24 noncarcinoma patients. No correlation between a positive lymph node finding and either the size or differentiation grade of the primary tumor or the presence of micrometastatic tumor cells in bone marrow assessed by immunocytochemistry with antikeratin monoclonal antibody CK2 was observed. Following a median observation time of 26.0 months (range, 15 to 39), patients with lymph node micrometastases showed a significantly shorter disease-free survival duration than node-negative patients (log-rank test, P = .005). The independence of this prognostic significance was demonstrated by a multivariate analysis (Cox regression model, P = .005).
  
  
  CONCLUSIONS
  Our results provide evidence that the presence of single lung carcinoma cells in lymph nodes is an independent indicator of the disseminatory capacity of an individual primary tumor. Immunohistochemical assessment of micrometastases in lymph nodes is recommended for current tumor staging in NSCLC, as it might lead to better stratification of patients for adjuvant therapy.
authors.affiliation: Department of Surgery, Klinikum Innenstadt, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Passlick
authors.forename: J R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: B
authors.initials: B
authors.lastname: Kubuschok
authors.forename: W
authors.initials: W
authors.lastname: Nathrath
authors.forename: O
authors.initials: O
authors.lastname: Thetter
authors.forename: U
authors.initials: U
authors.lastname: Pichlmeier
authors.forename: L
authors.initials: L
authors.lastname: Schweiberer
authors.forename: G
authors.initials: G
authors.lastname: Riethmüller
authors.forename: K
authors.initials: K
authors.lastname: Pantel
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D006023:Glycoproteins; D009363:Neoplasm Proteins