title: Immunohistochemical detection of occult lymph node metastases in non-small cell lung cancer: anatomical pathology results from Cancer and Leukemia Group B Trial 9761.
abstract: OBJECTIVE
  Our purpose was to study the detection of occult metastases (OM) in regional lymph nodes using immunohistochemical stain for cytokeratin, and for this study we targeted clinical stage I patients with non-small cell lung cancer.
  
  
  METHODS
  The study comprised the first 193 patients entered onto Cancer and Leukemia Group B protocol 9761. All had clinically staged T(1-2)N(0)M(0) non-small cell lung cancer, and all underwent curative resections of their primary tumors. Samples of the primary tumor and lymph nodes were taken from lymph node stations 2-12 and shipped to a central laboratory, where each lymph node was histologically processed and stained with H&E as well as with immunohistochemical stain using antibodies to cytokeratin (AE1/3).
  
  
  RESULTS
  Altogether, we examined 825 lymph nodes. Whereas routine H&E staining allowed us to detect 18 positive lymph nodes, immunohistochemical staining allowed us to detect 45 positive lymph nodes (P < 0.0001). There were 28 OM [i.e., those detectable only by immunohistochemistry (IHC)], and there was 1 metastasis detected only by H&E staining. The OM included 9 OM in N1 stations and 19 OM in N2 stations. Twelve patients with OM had skip metastases. Routine H&E staining upstaged six patients to N1, and IHC added another five. Routine H&E upstaged 9 patients to N2, and IHC added another 11. We also uncovered new details about the way in which H&E detection depends on metastatic tumor burden. Specifically, for the probability of detecting metastases by H&E to exceed 0.50, the maximum diameter of the metastasis must be greater than 0.23 mm.
  
  
  CONCLUSIONS
  IHC detects greater than twice as many positive regional lymph nodes as does H&E staining, and the foci of tumor it detects are significantly smaller than those detected by H&E staining.
authors.affiliation: Laboratory Medicine 113, VA Medical Center, Durham, North Carolina 27705, USA. voll002@duke.edu
authors.forename: Robin T
authors.initials: RT
authors.lastname: Vollmer
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Jonathan
authors.initials: J
authors.lastname: D'Cunha
authors.forename: Naif Z
authors.initials: NZ
authors.lastname: Abraham
authors.forename: Joette
authors.initials: J
authors.lastname: Solberg
authors.forename: Mitra
authors.initials: M
authors.lastname: Fatourechi
authors.forename: Ann
authors.initials: A
authors.lastname: Maruska
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kern
authors.forename: Mark R
authors.initials: MR
authors.lastname: Green
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kratzke
authors.forename: Michael A
authors.initials: MA
authors.lastname: Maddaus
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D009367:Neoplasm Staging