title: DNA ploidy measured on archived pretreatment biopsy material may correlate with prostate-specific antigen recurrence after prostate brachytherapy.
abstract: OBJECTIVE
  To explore whether DNA ploidy of prostate cancer cells determined from archived transrectal ultrasound-guided biopsy specimens correlates with disease-free survival.
  
  
  METHODS
  Forty-seven failures and 47 controls were selected from 1006 consecutive low- and intermediate-risk patients treated with prostate (125)I brachytherapy (July 1998-October 2003). Median follow-up was 7.5 years. Ten-year actuarial disease-free survival was 94.1%. Controls were matched using age, initial prostate-specific antigen level, clinical stage, Gleason score, use of hormone therapy, and follow-up (all P nonsignificant). Seventy-eight specimens were successfully processed; 27 control and 20 failure specimens contained more than 100 tumor cells were used for the final analysis. The Feulgen-Thionin stained cytology samples from archived paraffin blocks were used to determine the DNA ploidy of each tumor by measuring integrated optical densities.
  
  
  RESULTS
  The samples were divided into diploid and aneuploid tumors. Aneuploid tumors were found in 16 of 20 of the failures (80%) and 8 of 27 controls (30%). Diploid DNA patients had a significantly lower rate of disease recurrence (P=.0086) (hazard ratio [HR] 0.256). On multivariable analysis, patients with aneuploid tumors had a higher prostate-specific antigen failure rate (HR 5.13). Additionally, those with "excellent" dosimetry (V100 >90%; D90 >144 Gy) had a significantly lower recurrence rate (HR 0.25). All patients with aneuploid tumors and dosimetry classified as "nonexcellent" (V100 <90%; D90 <144 Gy) (5 of 5) had disease recurrence, compared with 40% of patients with aneuploid tumors and "excellent" dosimetry (8 of 15). In contrast, dosimetry did not affect the outcome for diploid patients.
  
  
  CONCLUSIONS
  Using core biopsy material from archived paraffin blocks, DNA ploidy correctly classified the majority of failures and nonfailures in this study. The results suggest that DNA ploidy can be used as a useful marker for aggressiveness of localized prostate cancer. A larger study will be necessary to further confirm our hypothesis.
authors.affiliation: Radiation Oncology, Provincial Prostate Brachytherapy Program, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. mkeyes@bccancer.bc.ca
authors.forename: Mira
authors.initials: M
authors.lastname: Keyes
authors.forename: Calum
authors.initials: C
authors.lastname: Macaulay
authors.forename: Malcolm
authors.initials: M
authors.lastname: Hayes
authors.forename: Jagoda
authors.initials: J
authors.lastname: Korbelik
authors.forename: W James
authors.initials: WJ
authors.lastname: Morris
authors.forename: Branko
authors.initials: B
authors.lastname: Palcic
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000782:Aneuploidy; D001918:Brachytherapy; D016022:Case-Control Studies; D004171:Diploidy; D018572:Disease-Free Survival; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D017211:Treatment Failure
chemical_list: D007457:Iodine Radioisotopes; D017430:Prostate-Specific Antigen