title: Changes in chromatin phenotype predict the response to hormonal deprivation therapy in patients with prostate cancer.
abstract: OBJECTIVE
  To assess the value of studying chromatin organization using high-resolution digital image analysis to predict the response to hormonal-deprivation therapy (HDT) in patients with prostate cancer, using pretreatment prostate tissues.
  
  
  METHODS
  A tissue microarray (TMA) was constructed using pretreatment paraffin-embedded tissues from transurethral resection of the prostate (TURP) samples (48 patients, 96 cores). None of the patients had received any treatment for prostate cancer before TURP. The patients' medical records for 5 years after treatment were assessed; patients were divided, based on their prostatic specific antigen (PSA) levels after treatment, into those optimally responsive to HDT (14) and those resistant to HDT (34). The latter were further subclassified based on their nadir PSA level. Imaging comprised a calibrated digital image-analysis system with software for densitometric and texture analysis, the latter being assessed on manually segmented nuclei (> or =30 nuclei/core).
  
  
  RESULTS
  Most of the measured digital texture features assessing chromatin density and distribution were significantly different between the prognostic groups (P = 0.001). In the training set, 12 of 14 HDT-responsive and 23 (68%) of HDT-resistant patients were accurately predicted. However, all HDT-resistant patients with a nadir PSA level of >5 ng/mL were accurately predicted. The overall classification sensitivity was 47%, specificity 94% with a positive predictive value of 85%. However, the sensitivity was 100% between patients optimally responsive to HDT and those poorly responsive with a nadir PSA level of >5 ng/mL.
  
  
  CONCLUSIONS
  Quantitative image analysis of chromatin phenotype showed promising value in predicting before treatment the response to HDT in patients diagnosed with prostatic adenocarcinoma. However, further work using larger data sets is required before adapting the technique in routine clinical practice.
authors.affiliation: Biomedical Imaging and Informatics Research Group, The Queen's University of Belfast, Belfast, Ireland. mahmoudmohamed@doctors.org.uk
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mohamed
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Greif
authors.forename: James
authors.initials: J
authors.lastname: Diamond
authors.forename: Osama
authors.initials: O
authors.lastname: Sharafeldin
authors.forename: Perry
authors.initials: P
authors.lastname: Maxwell
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Aidan
authors.initials: A
authors.lastname: O'Brien
authors.forename: Michael
authors.initials: M
authors.lastname: Young
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hamilton
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D002843:Chromatin / Q000473:pathology*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology / Q000628:therapy*; D010641:Phenotype; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D020728:Transurethral Resection of Prostate; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D002843:Chromatin