Java Web Start based software for automated quantitative nuclear analysis of prostate cancer and benign prostate hyperplasia

BackgroundAndrogen acts via androgen receptor (AR) and accurate measurement of the levels of AR protein expression is critical for prostate research. The expression of AR in paired specimens of benign prostate and prostate cancer from 20 African and 20 Caucasian Americans was compared to demonstrate an application of this system.MethodsA set of 200 immunopositive and 200 immunonegative nuclei were collected from the images using a macro developed in Image Pro Plus. Linear Discriminant and Logistic Regression analyses were performed on the data to generate classification coefficients. Classification coefficients render the automated image analysis software independent of the type of immunostaining or image acquisition system used. The image analysis software performs local segmentation and uses nuclear shape and size to detect prostatic epithelial nuclei. AR expression is described by (a) percentage of immunopositive nuclei; (b) percentage of immunopositive nuclear area; and (c) intensity of AR expression among immunopositive nuclei or areas.ResultsThe percent positive nuclei and percent nuclear area were similar by race in both benign prostate hyperplasia and prostate cancer. In prostate cancer epithelial nuclei, African Americans exhibited 38% higher levels of AR immunostaining than Caucasian Americans (two sided Student's t-tests; P < 0.05). Intensity of AR immunostaining was similar between races in benign prostate.ConclusionThe differences measured in the intensity of AR expression in prostate cancer were consistent with previous studies. Classification coefficients are required due to non-standardized immunostaining and image collection methods across medical institutions and research laboratories and helps customize the software for the specimen under study. The availability of a free, automated system creates new opportunities for testing, evaluation and use of this image analysis system by many research groups who study nuclear protein expression.

[1]  E. Barrack,et al.  Image analysis of androgen receptor immunostaining in metastatic prostate cancer heterogeneity as a predictor of response to hormonal therapy , 1993, Cancer.

[2]  M. Duffy,et al.  Objective measurement of breast cancer oestrogen receptor status through digital image analysis. , 2003, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[3]  J M Coggins,et al.  Semiautomated nuclear shape analysis of prostatic carcinoma and benign prostatic hyperplasia. , 1994, Analytical and quantitative cytology and histology.

[4]  F. S. French,et al.  Immunohistochemistry of the androgen receptor in human benign and malignant prostate tissue. , 1993, The Journal of urology.

[5]  Constantinos S. Pattichis,et al.  Computer-aided detection of breast cancer nuclei , 1997, IEEE Transactions on Information Technology in Biomedicine.

[6]  A. Seth,et al.  Computer based receptogram approach: an objective way of assessing immunohistochemistry of androgen receptor staining and its correlation with hormonal response in metastatic carcinoma of prostate , 2004, Journal of Clinical Pathology.

[7]  Thomas Wheeler,et al.  High Level of Androgen Receptor Is Associated With Aggressive Clinicopathologic Features and Decreased Biochemical Recurrence-free Survival in Prostate: Cancer Patients Treated With Radical Prostatectomy , 2004, The American journal of surgical pathology.

[8]  E. Olapade-Olaopa,et al.  Androgen receptor protein expression in prostatic tissues in black and caucasian men , 2004, The Prostate.

[9]  D. Horsfall,et al.  Detection of discrete androgen receptor epitopes in prostate cancer by immunostaining: measurement by color video image analysis. , 1994, Cancer research.

[10]  Yihua Xu,et al.  Nuclear-labeling index analysis (NLIA), a software package used to perform accurate automation of cell nuclear-labeling index analysis on immunohistochemically stained rat liver samples , 2000, Comput. Methods Programs Biomed..

[11]  P. Ekman,et al.  Microassays for androgen and progesterone receptor quantitation as compared with standard saturation analyses in human prostatic tissues , 2004, Urological Research.

[12]  Borivoj Vojnovic,et al.  An image analysis‐based approach for automated counting of cancer cell nuclei in tissue sections , 2003, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[13]  B. O’Malley,et al.  Molecular mechanisms of action of steroid/thyroid receptor superfamily members. , 1994, Annual review of biochemistry.

[14]  G. Prins,et al.  Image analysis of androgen receptor immunostaining in prostate cancer accurately predicts response to hormonal therapy. , 1998, Journal of Urology.

[15]  Desok Kim,et al.  Androgen receptor expression and cellular proliferation during transition from androgen-dependent to recurrent growth after castration in the CWR22 prostate cancer xenograft. , 2002, The American journal of pathology.

[16]  J. Mohler,et al.  A novel method for the analysis of the androgen receptor , 2002, Current urology reports.

[17]  Desok Kim,et al.  Immunohistochemical quantitation of androgen receptor expression using color video image analysis. , 1999, Cytometry.

[18]  Wojtek J. Krzanowski,et al.  Discrimination and Classification Using Both Binary and Continuous Variables , 1975 .

[19]  N. Otsu A threshold selection method from gray level histograms , 1979 .

[20]  D. S. Coffey,et al.  Computerized image analysis of nuclear shape as a prognostic factor for prostatic cancer , 1982, The Prostate.

[21]  Swaroop S Singh,et al.  Sampling strategy for prostate tissue microarrays for Ki-67 and androgen receptor biomarkers. , 2004, Analytical and quantitative cytology and histology.

[22]  P. Walsh,et al.  Hormonal Therapy of Prostatic Cancer , 1980, Cancer.

[23]  A. Jemal,et al.  Cancer Statistics, 2005 , 2005, CA: a cancer journal for clinicians.

[24]  Desok Kim,et al.  Racial differences in androgen receptor protein expression in men with clinically localized prostate cancer. , 2003, The Journal of urology.

[25]  A. Partin,et al.  Prediction of prognosis in untreated stage A2 prostatic carcinoma , 1992, Cancer.

[26]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[27]  R W Veltri,et al.  Quantitative nuclear grade (QNG): A new image analysis‐based biomarker of clinically relevant nuclear structure alterations , 2000, Journal of cellular biochemistry. Supplement.

[28]  Rebecca J Blatt,et al.  Automated quantitative analysis of angiogenesis in the rat aorta model using Image-Pro Plus 4.1 , 2004, Comput. Methods Programs Biomed..