title: A DNA cytometric proliferation index improves the value of the DNA ploidy pattern as a prognosticating tool in patients with carcinoma of the prostate.
abstract: OBJECTIVE
  A still controversial issue is whether the results of a cytometric assessment of the DNA distribution pattern of the nuclei of the neoplastic parenchymal cells of a prostatic adenocarcinoma has additional prognostic value to that of the stage and grade of the disease. To increase the accuracy of the DNA ploidy assessments. Image cytometry (ICM) has been used and combined with the determination of an ICM proliferation index (PI) to increase its value as an additional prognosticating tool.
  
  
  METHODS
  We investigated 96 patients, followed up since diagnosis in 1980/1981 until death or, in 11 surviving patients, for an average of 14.5 years. Survival analysis was made by the conventional Kaplan-Meier method. Fine-needle aspiration biopsy was used as the major diagnostic tool. The neoplastic cell nuclei were classified as ICM DNA diploid, tetraploid, or aneuploid by means of the ploidy-establishing peak in the ICM DNA histograms, as well as the fraction of tumor cells in the S-phase. Scattered cells to the right of the ploidy-establishing peak, the S-phase fraction, and those in the G2M area of the ICM DNA histograms were counted as percent of the total number of tumor cells; this percentage was defined as the PI. Arbitrarily, tumors with a PI less than 5% were classified as having a low proliferation rate, those with a PI greater than 10% were considered highly proliferating, and those with a PI between 5% and 10% as carcinomas with an intermediate proliferation potency.
  
  
  RESULTS
  By univariate analyses, clinical stage, cytodiagnostic grade, cytometric DNA ploidy pattern and PI all had significant prognostic value. By multivariate analyses, the PI was found to add prognostic information to that of the ICM DNA ploidy pattern variable, giving it an increase in its statistical P value from 0.002 to 0.0005. As a consequence, the combination of these two variables was found to give rise to three new patient groups with regards to their prognosis: DNA group I had tumors with a diploid ICM DNA pattern with a low PI; DNA group II had tumors with a diploid or tetraploid ICM DNA tumor cell nuclei pattern with an intermediate PI; and DNA group III had a diploid or tetraploid ICM DNA pattern with high PI and all tumors with an aneuploid pattern. By multivariate analysis, including tumor grade and clinical stage, these new DNA groups (P = 0.0004) and M stage disease (P = 0.0006) were the only significant prognostic variables.
  
  
  CONCLUSIONS
  A DNA cytometric PI improves the prognosticating value of DNA ploidy. Patients with prostatic adenocarcinomas, classified as DNA group I, have a low risk of death from their neoplastic disease with deferred or hormonal treatment only.
authors.affiliation: Department of Urology, University of Lund, University Hospital, Malmo, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Ahlgren
authors.forename: K
authors.initials: K
authors.lastname: Lindholm
authors.forename: U
authors.initials: U
authors.lastname: Falkmer
authors.forename: P A
authors.initials: PA
authors.lastname: Abrahamsson
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002455:Cell Division; D004273:DNA, Neoplasm / Q000032:analysis; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011003:Ploidies; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm