| 1. |
- Tomlins, Scott A., et al.
(författare)
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The role of SPINK1 in ETS rearrangement-negative prostate cancers
- 2008
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Ingår i: Cancer Cell. - Amsterdam : Elsevier. - 1535-6108 .- 1878-3686. ; 13:6, s. 519-28
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Tidskriftsartikel (refereegranskat)abstract
- ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers ( approximately 10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.
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| 2. |
- Bjartell, Anders, et al.
(författare)
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Association of cysteine-rich secretory protein 3 and beta-microseminoprotein with outcome after radical prostatectomy
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 13:14, s. 4130-4138
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: It has been suggested that cysteine-rich secretory protein 3 (CRISP-3) and p-microseminoprotein (MSP) are associated with outcome in prostate cancer. We investigated whether these markers are related to biochemical recurrence and whether addition of the markers improves prediction of recurring disease. Experimental Design: Tissue microarrays of radical prostatectomy specimens were analyzed for CRISP-3 and MSP by immunohistochemistry. Associations between marker positivity and postprostatectomy biochemical recurrence [prostate-specific antigen (PSA) > 0.2 ng/mL with a confirmatory level] were evaluated by univariate and multivariable Cox proportional hazards regression. Multivariable analyses controlled for preoperative PSA and pathologic stage and grade. Results: Among 945 patients, 224 had recurrence. Median follow-up for survivors was 6.0 years. Patients positive for CRISP-3 had smaller recurrence-free probabilities, whereas MSP-positive patients had larger recurrence-free probabilities. On univariate analysis, the hazard ratio for patients positive versus negative for CRISP-3 was 1.53 (P =0.010) and for MSP was 0.63 (P = 0.004). On multivariable analysis, both CRISP-3 (P = 0.007) and MSP (P = 0.002) were associated with recurrence. The hazard ratio among CRISP-3-positive/MSP-negative patients compared with CRISP-3-negative/MSP-positive patients was 2.38. Adding CRISP-3 to a base model that included PSA and pathologic stage and grade did not enhance the prediction of recurrence, but adding MSP increased the concordance index minimally from 0.778 to 0.781. Conclusion: We report evidence that CRISP-3 and MSP are independent predictors of recurrence after radical prostatectomy for localized prostate cancer. However, addition of the markers does not importantly improve the performance of existing predictive models. Further research should aim to elucidate the functions of CRISP-3 and MSP in prostate cancer cells.
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| 3. |
- Carlsson, Sigrid, 1982, et al.
(författare)
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Pathological Features of Lymph Node Metastasis for Predicting Biochemical Recurrence After Radical Prostatectomy for Prostate Cancer.
- 2013
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Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 189:4, s. 1314-1319
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Subclassification of nodal stage may have prognostic value in men with lymph node metastasis at radical prostatectomy. We explored the role of extranodal extension, size of the largest metastatic lymph node and the largest metastasis, and lymph node density as predictors of biochemical recurrence. MATERIALS AND METHODS: We reviewed pathological material from 261 patients with node positive prostate cancer. We examined the predictive value when adding the additional pathology findings to a base model including extraprostatic extension, seminal vesicle invasion, radical prostatectomy Gleason score, prostate specific antigen and number of positive lymph nodes using the Cox proportional hazards regression and Harrell concordance index. RESULTS: The median number of lymph nodes removed was 14 (IQR 9, 20) and the median number of positive lymph nodes was 1 (IQR 1, 2). At a median followup of 4.6 years (IQR 3.2, 6.0) 155 of 261 patients experienced biochemical recurrence. The mean 5-year biochemical recurrence-free survival rate was 39% (95% CI 33-46). Median diameter of the largest metastatic lymph node was 9 mm (IQR 5, 16). On Cox regression radical prostatectomy specimen Gleason score (greater than 7 vs 7 or less), number of positive lymph nodes (3 or greater vs 1 or 2), seminal vesicle invasion and prostate specific antigen were associated with significantly increased risks of biochemical recurrence. On subset analysis metastasis size significantly improved model discrimination (base model Harrell concordance index 0.700 vs 0.655, p = 0.032). CONCLUSIONS: Our study confirms that the number of positive lymph nodes is a predictor of biochemical recurrence in men with node positive disease. The improvement in prognostic value of measuring the metastatic focus warrants further investigation.
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| 4. |
- Fine, Samson W., et al.
(författare)
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A Contemporary Update on Pathology Reporting for Prostate Cancer: Biopsy and Radical Prostatectomy Specimens
- 2012
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 62:1, s. 20-39
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Forskningsöversikt (refereegranskat)abstract
- Context: The diagnosis of and reporting parameters for prostate cancer (PCa) have evolved over time, yet they remain key components in predicting clinical outcomes. Objective: Update pathology reporting standards for PCa. Evidence acquisition: A thorough literature review was performed for articles discussing PCa handling, grading, staging, and reporting published as of September 15, 2011. Electronic articles published ahead of print were also considered. Proceedings of recent international conferences addressing these areas were extensively reviewed. Evidence synthesis: Two main areas of reporting were examined: (1) prostatic needle biopsy, including handling, contemporary Gleason grading, extent of involvement, and high-risk lesions/precursors and (2) radical prostatectomy (RP), including sectioning, multifocality, Gleason grading, staging of organ-confined and extraprostatic disease, lymph node involvement, tumor volume, and lymphovascular invasion. For each category, consensus views, controversial areas, and clinical import were reviewed. Conclusions: Modern prostate needle biopsy and RP reports are extremely detailed so as to maximize clinical utility. Accurate diagnosis of cancer-specific features requires up-to-date knowledge of grading, quantitation, and staging criteria. While some areas remain controversial, efforts to codify existing knowledge have had a significant impact on pathology practice. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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