title: Quantification of tumor cell burden by analysis of single cell lymph node disaggregates in metastatic prostate cancer.
abstract: BACKGROUND
  The size of lymph node (LN) metastases in prostate cancer patients represents an important prognosticator, but histological work-up may not reflect the true extent of tumor invasion. We present a novel technique (1) to detect early tumor cell dissemination and (2) to quantify the true tumor burden.
  
  
  METHODS
  Prospectively 232 LN of 20 consecutive patients with prostate cancer after lymph node dissection were longitudinally bisected, one half was subjected to single cell immunocytochemistry for pancytokeratine (CK), the other half underwent routine histopathological work-up and step section analysis. In immunocytochemistry, tumor cell density (TCD) was quantified by calculating the number of CK-positive cells/million leucocytes and compared to routine histopathology and step section analysis.
  
  
  RESULTS
  Eight of 20 patients were positive in histopathology and step sectioning, but 14 of 20 patients were positive in single cell analysis. Twenty-five of 232 LN were positive in routine histopathology, whereas 52 of 232 LN were positive in single cell analysis. Median TCD in histopathologically positive LN was 3060.0 x 10(-6) and 9.9 x 10(-6) in histopathologically negative LN (P < 0.0001). Mean TCD of histopathologically negative LN of pN1 patients was significantly higher than the mean TCD of pN0 patients (P < 0.003). Mean TCD per patient correlated with serum-PSA (r(2) = 0.48, P < 0.006).
  
  
  CONCLUSIONS
  Single cell analysis has an increased detection rate compared to routine histopathology and even to serial step section analysis. The method can detect early tumor dissemination and enables quantification of the tumor burden. The subgroup of histopathologically negative LN with CK-positive cells represents tumor cell dissemination not depicted histologically.
authors.affiliation: Department of Urology, Eberhard-Karls-University, Tuebingen, Germany. david.schilling@med.uni-tuebingen.de
authors.forename: David
authors.initials: D
authors.lastname: Schilling
authors.forename: Joerg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Karl
authors.initials: K
authors.lastname: Sotlar
authors.forename: Ursula
authors.initials: U
authors.lastname: Kuehs
authors.forename: Erika
authors.initials: E
authors.lastname: Senger
authors.forename: Udo
authors.initials: U
authors.lastname: Nagele
authors.forename: Ulf
authors.initials: U
authors.lastname: Boekeler
authors.forename: Anja
authors.initials: A
authors.lastname: Ulmer
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000368:Aged; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D016014:Linear Models; D008197:Lymph Node Excision / Q000379:methods; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
chemical_list: D007633:Keratins