Changes in chromatin phenotype predict the response to hormonal deprivation therapy in patients with prostate cancer

• Published in: BJU international 2009-02, Vol.103 (3), p.391-398
• Main Authors: Mohamed, Mahmoud, Greif, Philipp A., Diamond, James, Sharafeldin, Osama, Maxwell, Perry, Montironi, Rodolfo, O’Brien, Aidan, Young, Michael, Hamilton, Peter W.
• Format: Article
• Language: English
• Subjects: Androgen Antagonists - therapeutic use; Biological and medical sciences; chromatin; Chromatin - pathology; Gynecology. Andrology. Obstetrics; hormonal treatment; Humans; Male; Male genital diseases; Medical sciences; Microarray Analysis; Neoplasms, Hormone-Dependent - pathology; Neoplasms, Hormone-Dependent - therapy; Nephrology. Urinary tract diseases; Phenotype; Prognosis; prostate; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; texture; Transurethral Resection of Prostate; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2008.08063.x

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. MATERIALS AND 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 (≥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. CONCLUSION 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.