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- Häggarth, Lars, et al.
(författare)
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Diagnostic biomarkers of prostate cancer
- 2011
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 45:1, s. 60-67
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Diagnostic tissue biomarkers for prostate cancer (PC) include basal cell markers and alpha-methylacyl-coenzyme A-racemase (AMACR), often used in combination. Their sensitivity and specificity are not perfect and there is a need for additional diagnostic biomarkers for PC in cases that are difficult to diagnose on routine stained sections. Material and methods. This study investigated the diagnostic accuracy of three novel tissue biomarkers for PC found through a search in the Human Protein Atlas database (www.proteinatlas.com): somatic cytochrome c (CYCS), intestinal cell kinase (ICK) and inhibitor of nuclear factor-kappa B kinase subunit beta (IKBKB), and compared the results with AMACR. A tissue microarray was constructed from 40 consecutive radical prostatectomy (RP) specimens including benign prostatic tissue, atrophy, high-grade prostatic intraepithelial neoplasia (HGPIN) and PC. Immunoreactivity was scored based on staining intensity and extent. Real-time polymerase chain reaction (PCR) was performed on malignant and benign frozen tissue samples from 32 RP specimens. Results. All four biomarkers showed a stronger expression in PC and HGPIN than in benign tissue (p < 0.001). The highest diagnostic accuracy for PC was achieved with ICK and AMACR at 97%. The area under the curve for CYCS, ICK, IKBKB and AMACR was 0.859, 0.997, 0.865 and 0.983, respectively. The presence of mRNA transcripts of the genes was confirmed by real-time PCR in benign and malignant prostatic tissue. Conclusions. AMACR is an accurate diagnostic tissue marker for PC. However, in some PCs AMACR is false negative and a panel of CYCS, ICK and IKBKB may serve as ancillary diagnostic tool.
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| 4. |
- Jaraj, Sara Jonmarker, et al.
(författare)
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GAD1 is a biomarker for benign and malignant prostatic tissue
- 2011
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 45:1, s. 39-45
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Tissue-specific markers are useful for identification of tumour type in advanced cancers of unknown origin. This study investigated the expression of glutamate decarboxylase 1 (GAD1) in prostate and control tissue compared with the established prostate-specific markers prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA). Material and methods. A tissue microarray was constructed of 36 prostate adenocarcinomas, eight benign prostate samples and benign and malignant control tissues from urinary bladder, lung and rectum. Immunohistochemistry for GAD 1, PSA and PSMA was performed. The products of staining intensity and extent were analysed. The GAD1 antibody was validated by Western blot. Real-time polymerase chain reaction (RT-PCR) was performed on malignant and benign samples from each tissue type. Results. GAD 1 and PSA immunostains were significantly stronger in malignant and benign prostatic tissue than in controls. PSMA was stronger in prostate cancer than in urothelial and rectal cancer but had a lower specificity than GAD1 and PSA. GAD I expression decreased with increasing Gleason score. RT-PCR confirmed the presence of mRNA for GAD I, PSA and PSMA in prostate samples. Conclusion. GAD1 is expressed in benign and malignant prostatic tissue and may serve as a highly prostate-specific tissue biomarker.
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| 5. |
- Häggarth, Lars
(författare)
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Biopsies, diagnosis and prognosis in prostate cancer
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer is the third most common cancer in men worldwide, and poses a challenge both for patients and health care systems. Many aspects of prostate cancer are controversial, from screening for early detection to the concept of insignificant cancer that does not need curative treatment. This study deals with different aspects of the diagnostic process, including biopsy procedures, histopathological diagnosis and biomarkers for carcinogenesis and progression. Biopsies of the prostate are the prerequisite for histopathological diagnosis of cancer. The standard biopsy instrument uses an inner needle with a side-notch. The tissue yield of a novel end-cutting instrument was investigated and compared with that of the standard instrument. The new instrument provided thicker biopsies, flatter embedding in paraffin blocks and an optional greater stroke length. These advantages were countered by loss of some biopsy cores. The new instrument can be recommended primarily for men with large prostates or repeat biopsies when there is a persistent serum PSA elevation and suspicion of anterior tumour. Tumour volume of prostate cancer correlates with progression after radical prostatectomy, but its clinical utility is limited by difficulties in the preoperative assessment. The prediction of large volume prostate cancer by prostate biopsies was studied. Biopsy cancer length and percentage cancer length predicted large tumours better than number and percentage of cores positive for cancer. A cancer length of 30 mm predicted a tumour volume of >4 ml in 95% of cases. Gleason score and serum PSA were weaker predictors. Tumour volumes of <4 ml were found in as many as 35% of men with 6 biopsy cores, indicating that number of positive cores is less useful than linear cancer extent as predictor of large tumours. DNA ploidy status correlates to stage and outcome, but studies on its clinical utility have shown divergent results. The impact of tumour heterogeneity on preoperative ploidy assessment in prostate cancer was investigated by comparing DNA ploidy of prostate biopsies with radical prostatectomy specimens that had been mapped for ploidy heterogeneity. Ploidy was both under- and overestimated in biopsies, and this finding was more pronounced in tumours with heterogeneous ploidy status. Accuracy increased with multiple biopsies. Oxidative stress is considered to be of great importance in the development of prostate cancer. The expression of three proteins in the redox control system was investigated, in order to evaluate their involvement in prostate cancer. By immunohistochemistry on prostate tissue microarrays all three proteins showed similar expression patterns with the highest immunoreactivity in HGPIN followed by atrophy, cancer and benign tissue. No correlation with biochemical recurrence was found. In patients with metastatic cancer it is important for treatment and prognosis to assess the site of tumour origin. The origin of certain tumour types is difficult to identify by morphology alone or with existing biomarkers. In a database search for new prostate-specific markers, GAD1 was identified. Its tissue specificity was investigated in a tissue microarray and compared with PSA and PSMA. GAD1 showed a high specificity and sensitivity to benign and malignant prostate tissue and was almost entirely negative in cancers from lung, rectum and urinary bladder, i.e. tumours that may be considered as differential diagnoses to advanced prostate cancer. In a database search for diagnostic markers with ability to discriminate between malignant and benign prostate tissue, four proteins were identified: AMACR, CYCS, ICK and IKBKB. AMACR is a well- established diagnostic biomarker, but is negative in some prostate cancers and may also be false positive. The expression was analysed in a tissue microarray of benign prostatic tissue, precursor lesions and cancer from the same cases. All four markers showed a stronger expression in prostate cancer and HGPIN than in benign tissue. A panel of diagnostic biomarkers may serve as an adjunct tool for diagnosis of difficult cases.
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