| 1. |
- Dumke, Christoph, et al.
(författare)
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SATB1, genomic instability and Gleason grading constitute a novel risk score for prostate cancer
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Current prostate cancer risk classifications rely on clinicopathological parameters resulting in uncertainties for prognostication. To improve individual risk stratification, we examined the predictive value of selected proteins with respect to tumor heterogeneity and genomic instability. We assessed the degree of genomic instability in 50 radical prostatectomy specimens by DNA-Image-Cytometry and evaluated protein expression in related 199 tissue-microarray (TMA) cores. Immunohistochemical data of SATB1, SPIN1, TPM4, VIME and TBB5 were correlated with the degree of genomic instability, established clinical risk factors and overall survival. Genomic instability was associated with a GS >= 7 (p = 0.001) and worse overall survival (p = 0.008). A positive SATB1 expression was associated with a GS <= 6 (p = 0.040), genomic stability (p = 0.027), and was a predictor for increased overall survival (p = 0.023). High expression of SPIN1 was also associated with longer overall survival (p = 0.048) and lower preoperative PSA-values (p = 0.047). The combination of SATB1 expression, genomic instability, and GS lead to a novel Prostate Cancer Prediction Score (PCP-Score) which outperforms the current D'Amico et al. stratification for predicting overall survival. Low SATB1 expression, genomic instability and GS >= 7 were identified as markers for poor prognosis. Their combination overcomes current clinical risk stratification regimes.
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| 2. |
- Glaessgen, Axel
(författare)
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Markers of differentiation and prognosis in prostate cancer : a morphological and immunohistochemical study
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer (PCa) is the most common malignancy in men worldwide. The disease shows a wide range of patient outcome between indolent and highly aggressive tumor behavior. Prognostic factors are needed to stratify PCa patients in different prognostic groups for treatment decision and to predict outcome. Today serum prostate specific antigen (PSA), TNM staging and histomorphological prognostic factors such as the Gleason score (GS) are used in clinical practice for prediction of prognosis. Despite its powerful prognostic power, the utility of GS has decreased in the last decades due to a grade and stage shift. Efforts have been made to develop the GS and modified systems such as percent Gleason grade 4/5 (%GG4/5) and modified Gleason score (mGS) have been suggested. Almost monthly new potential biomarkers for PCa are reported but most of them will have only very limited clinical impact. To be useful, a marker must provide prognostic information, which is independent from that of established prognostic factors, its reproducibility must be satisfactory and the information obtained clinically relevant. The interobserver reproducibility of the conventional GS, %GG4/5 and mGS was analyzed among four uropathologists. The overall reproducibility of %GG4/5 and mGS was at least as good as that of the GS. However, clustering of mGS in odd scores was found and severe disagreement was more common than with GS. The ability of prostate needle biopsies to correctly predict %GG4/5 in prostatectomy specimens was found to be almost as good as for GS. We investigated the expression of pancreatic duodenal homeobox-1 (PDX-1) and heat shock proteins (HSP) 27, 60 and 70 in prostate tissue. Tissue microarrays (TMA) were constructed for analysis of prognostic value (289 PCas, median follow-up 48.9 months),expression in benign tissues, high-grade PIN, primary PCa and lymph node metastases. Two independent observers evaluated intensity and extent of immunohistochemical staining. HSP 27 and 60, but not PDX-1 and HSP 70, correlated with biochemical recurrence. In a multivariate analysis including histological prognostic factors HSP 60 was an independent predictor of recurrence. PDX-1 was overexpressed in cancer vs. benign tissue, but also in atrophy and high-grade PIN. PDX-1 decreased with higher Gleason pattern and in metastases. There was only slight interobserver agreement for extent of immunoreactivity of PDX-1 and HSPs but moderate to substantial agreement for intensity of the staining. Thus, the question was raised whether staining extent shouldbe estimated on TMA. Presence of PDX-1 protein in benign and malignant prostatic tissue was confirmed by Western blot. In conclusion we suggest that HSP 27 and HSP 60 are predictors of biochemical recurrence after radical prostatectomy and PDX-1 is of potential interest in the pathogenesis of PCa.
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| 3. |
- Glaessgen, Axel, et al.
(författare)
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Prediction of percent Gleason grade 4/5 by multiple core biopsies
- 2006
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 40:6, s. 465-471
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate whether percent Gleason grade 4/5 (i.e. the proportion of a tumor occupied by high-grade cancer) can be predicted by multiple needle biopsies. Material and methods. In 115 men, 8-14 (mean 10) biopsies were taken, including eight from standardized positions (apex, mid-medial, mid-lateral and base). Biopsies were reviewed and cancer lengths measured. All men underwent radical prostatectomy. The prostatectomy specimens were totally embedded and tumor volume measured planimetrically. Gleason scores and percent Gleason grade 4/5 were assessed for both biopsy and prostatectomy specimens. Results. Percent Gleason grade 4/5 in prostatectomy specimens was predicted correctly in 34% of cases and within 10%, 20% and 30% in 55%, 64% and 73% of cases, respectively. Biopsies had a sensitivity, specificity and accuracy for Gleason grade 4/5 of 62%, 87% and 69%, respectively. Positive and negative predictive values were 93% and 45%, respectively. The weighted kappa value for agreement was slightly higher for Gleason score (0.685) than for percent Gleason grade 4/5 (0.573). The univariate correlation for percent Gleason grade 4/5 in biopsies and the main tumor was r = 0.62, r(2) = 0.39 (p < 0.001). In univariate logistic regression, percent Gleason grade 4/5 on biopsies predicted the presence of any Gleason grade 4/5 cancer in the main tumor (p = 0.009). Conclusions. Gleason grade 4/5 in prostatectomy specimens correlates with findings in preoperative biopsies. Whether this measure will be used in routine practice remains to be seen.
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| 4. |
- Rubio, Carlos A., et al.
(författare)
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Quantitative assessment of the subepithelial collagen band does not increase the accuracy of diagnosis of collagenous colitis
- 2008
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Ingår i: American Journal of Clinical Pathology. - 0002-9173 .- 1943-7722. ; 130:3, s. 375-381
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Tidskriftsartikel (refereegranskat)abstract
- The thickness of eosinophilic band in collagenous colitis (CC) was assessed by 3 methods: histologic estimates (22 observers), conventional measurements using a calibrated micrometric scale (1 observer), and semiautomatic micrometric measurements (1 observer). By the histologic estimate technique, 7.4% of the results failed to diagnose CC; by calibrated micrometry, the failure was 6% and by semiautomatic micrometry, 6%. The main difficulty in measuring the thickness of the CC band is that the deeper border of the band appears fuzzy and hairy-irregular. CC should be defined not exclusively on the basis of the thickness of the collagen table, but as a microscopic constellation characterized by a distorted superficial cell arrangement, with areas of epithelial denudation and inflammatory cells in the superficial epithelium and the lamina propria. In agreement with Lazenby's statement: "Focusing solely on the collagen band can result in both over- and underdiagnosis"
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