title: Dedifferentiation in the metastatic progression of prostate carcinoma.
abstract: BACKGROUND
  Dedifferentiation is a distinctive feature of cancer progression. Detailed histologic analysis of primary prostate carcinoma and synchronous lymph node metastases may improve our understanding of the complex process of cancer progression and metastasis.
  
  
  METHODS
  The authors studied 242 regional lymph node positive prostate carcinoma patients who underwent radical prostatectomy and bilateral lymphadenectomy between 1987 and 1992 at the Mayo Clinic. Patients ranged in age from 47-79 years (median, 66 years). The median follow-up was 6.1 years. Gleason scores of lymph node metastases and primary tumors were compared and correlated with systemic disease progression. Histologic dedifferentiation was defined as a higher Gleason grade in the lymph node metastases than in the primary tumor. Systemic disease progression was defined as the presence of distant metastases documented by biopsies, abdominal computed tomography, plain radiograph, or bone scan.
  
  
  RESULTS
  The 5-year systemic progression free survival (PFS) rate was 90%. The Gleason score in the lymph node metastases was higher than in the primary tumor in 45% of patients, lower in 12% of patients, and matched exactly in 43% of patients. The 5-year PFS was significantly different between patients with histologic dedifferentiation (88% +/- 3) and those without dedifferentiation (94% +/- 2) (P = 0.04). Adjusting for the Gleason grade of the primary tumor and total lymph node tumor volume, the relative risk for disease progression associated with dedifferentiation was 1.8 (95% confidence interval, 0.7-4.7; P = 0.25).
  
  
  CONCLUSIONS
  The findings of the current study demonstrate the morphologic heterogeneity of metastases from prostate carcinoma. There is a trend toward histologic dedifferentiation when prostate carcinoma metastasizes to regional lymph nodes. This dedifferentiation, although univariately significant, was not associated with disease progression when adjusted for lymph node tumor volume.
authors.affiliation: Department of Pathology and Urology, Indiana University School of Medicine, Indianapolis, Indiana, USA. lcheng@inpui.edu
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: J
authors.initials: J
authors.lastname: Slezak
authors.forename: E J
authors.initials: EJ
authors.lastname: Bergstralh
authors.forename: J C
authors.initials: JC
authors.lastname: Cheville
authors.forename: S
authors.initials: S
authors.lastname: Sweat
authors.forename: H
authors.initials: H
authors.lastname: Zincke
authors.forename: D G
authors.initials: DG
authors.lastname: Bostwick
mesh_terms: D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000145:classification / Q000473:pathology*; D012189:Retrospective Studies