title: A pragmatic approach to the diagnosis of nodal micrometastases in early stage non-small cell lung cancer.
abstract: BACKGROUND
  This study was designed to develop a both sensitive and efficient algorithm for detection of lymph node micrometastases and to determine its prognostic impact in patients with early stage non-small cell lung cancer (NSCLC).
  
  
  METHODS
  One hundred seventy patients with NSCLC p stage I and II were included in this study, of which n = 5299 lymph nodes were obtained and submitted to histopathologic analysis. From each patient, a median number of 31 lymph nodes was received (N-1 position: median n = 16; N-2 position: median n = 15). Immunohistochemistry was performed to detect micrometastases unobvious by conventional microscopy using antibodies against cytokeratins (CK) (pan-CK: KL-1, CK 5/6, CK 7) and the epithelial marker Ber-EP4.
  
  
  RESULTS
  In 82 patients (48.2%), micrometastases were revealed in immunohistochemistry staining. KL-1 detected micrometastases in 201 (99.5%) of 202 positive lymph nodes. Subsequently, this resulted in an upstaging in 39 patients (20.5%). Detection of micrometastases in otherwise tumor-free N2-lymph nodes had a significant prognostic impact (mean disease-free survival 21.4 versus 45.3 months, p = 0.022), affecting 4.7% of patients. Survival differences between patients who were upstaged into stage II (N0>N1) and those remaining in stage I were not statistically significant (p = 0.537).
  
  
  CONCLUSIONS
  Extended workup of N2-lymph nodes using one broad-spectrum keratin marker in otherwise N2-negative lymph nodes may represent a both efficient and sensitive approach to the identification of micrometastases in dissected lymph nodes of patients with early stage NSCLC.
authors.affiliation: Department of General Pathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.forename: Thomas
authors.initials: T
authors.lastname: Muley
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
authors.forename: Elisa
authors.initials: E
authors.lastname: Palm
authors.forename: Dörthe
authors.initials: D
authors.lastname: Kieslich de Hol
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
authors.forename: Konstantina
authors.initials: K
authors.lastname: Storz
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Schnabel
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.forename: Hans
authors.initials: H
authors.lastname: Hoffmann
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism / Q000601:surgery; D009367:Neoplasm Staging; D018307:Neoplasms, Squamous Cell / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor