Abstract
Prostate carcinoma is the most common cancer in men with few, quantifiable, biomarkers. Prostate cancer biomarker discovery has been hampered due to subjective analysis of protein expression in tissue sections. An unbiased, quantitative immunohistochemical approach provided here, for the diagnosis and stratification of prostate cancer could overcome this problem. Antibodies against four proteins BTF3, HINT1, NDRG1 and ODC1 were used in a prostate tissue array (> 500 individual tissue cores from 82 patients, 41 case pairs matched with one patient in each pair had biochemical recurrence). Protein expression, quantified in an unbiased manner using an automated analysis protocol in ImageJ software, was increased in malignant vs non-malignant prostate (by 2-2.5 fold, p<0.0001). Operating characteristics indicate sensitivity in the range of 0.68 to 0.74; combination of markers in a logistic regression model demonstrates further improvement in diagnostic power. Triple-labeled immunofluorescence (BTF3, HINT1 and NDRG1) in tissue array showed a significant (p<0.02) change in co-localization coefficients for BTF3 and NDRG1 co-expression in biochemical relapse vs non-relapse cancer epithelium. BTF3, HINT1, NDRG1 and ODC1 could be developed as epithelial specific biomarkers for tissue based diagnosis and stratification of prostate cancer.
Highlights
Prostate carcinoma is a disease of the epithelium, the most common cancer in men and the cause of considerable morbidity and mortality [1]
BTF3, HINT1, NDRG1 and Ornithine decarboxylase 1 (ODC1) in malignant cores, diagnosed by histopathology, compared to non-malignant cores (p
By using global gene expression analysis, tremendous progress has been made in the identification of dysregulated genes in prostate cancer over the past decade
Summary
Prostate carcinoma is a disease of the epithelium, the most common cancer in men and the cause of considerable morbidity and mortality [1]. Over 30,000 men are diagnosed of prostate cancer and over 10,000 die of the disease in the UK. In 2010, 217,730 new cases of prostate cancer were diagnosed in the US, with 32,050 American males dying of the disease [2]. Diagnosis and prognosis of prostate cancer is based on tissue morphology from biopsies (~1 million procedures in USA and ~70,000 in the UK / year). First time biopsies identify cancer in 38% of cases whereas equivocal diagnosis or false negatives constitute ~25-30% of cases [3]. Descriptors of aggressiveness (e.g. Gleason grade) determine cancer management and therapy but have significant drawbacks and high variance, for low grade cancers
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