Explore the vast range of titles available.

Y-box binding protein 1 (YB-1) is an RNA and DNA binding factor with potential prognostic cancer. To evaluate the clinical impact of YB-1, a tissue microarray with 11,152 prostate cancers was analysed by immunohistochemistry. Cytoplasmic and nuclear staining was separately analysed. Cytoplasmic YB-1 was absent or weak in normal epithelium but seen in 86,3% of carcinomas. Cytoplasmic staining was weak, moderate, and strong in 29.6%, 43.7% and 13.0% of tumours and was accompanied by nuclear YB-1 staining in 32.1% of cases. Particularly nuclear staining was strongly linked to poor patient prognosis (p < 0.0001). YB-1 protein was more abundant in ERG positive (95.1%) than in ERG negative cancers (80.4%; p < 0.0001), but any prognostic impact of YB-1 staining was limited to the ERG-negative subset. Similarly, significant associations with pT stage and Gleason grade (p < 0.0001 each) were driven by the ERG negative subset. The significant association of YB-1 protein detection with deletions of PTEN , 5q21 and 6q15 fits well in the protein’s role as an inhibitor of DNA damage dependent cell cycle arrest, a role that is likely to induce genomic instability. In summary, the data show, that the prognostic impact of YB-1 expression is limited to ERG negative prostate cancers.

Background Animal model experiments have suggested a role of the DNA repair protein ERCC1 (Excision Repair Cross-Complementation Group 1) in prostate cancer progression. Methods To better understand the impact of ERCC1 protein expression in human prostate cancer, a preexisting tissue microarray (TMA) containing more than 12,000 prostate cancer specimens was analyzed by immunohistochemistry and data were compared with tumor phenotype, PSA recurrence and several of the most common genomic alterations ( TMPRSS2:ERG fusions: deletions of PTEN , 6q, 5q, 3p). Results ERCC1 staining was seen in 64.7% of 10,436 interpretable tissues and was considered weak in 37.1%, moderate in 22.6% and strong in 5% of tumors. High-level ERCC1 staining was linked to advanced pT stage, high Gleason grade, positive lymph nodes, high pre-operative serum PSA, and positive surgical margin status ( p  < 0.0001 each). High ERCC1 expression was strongly associated with an elevated risk of PSA recurrence ( p  < 0.0001). This was independent of established prognostic features. A subgroup analysis of cancers defined by comparable quantitative Gleason grades revealed that the prognostic impact was mostly driven by low-grade tumors with a Gleason 3 + 3 or 3 + 4 (Gleason 4: ≤5%). High ERCC1 expression was strongly associated with the presence of genomic alterations and expression levels increased with the number of deletions present in the tumor. These latter data suggest a functional relationship of ERCC1 expression with genomic instability. Conclusion The results of our study demonstrate that expression of ERCC1 - a potential surrogate for genomic instability - is an independent prognostic marker in prostate cancer with particular importance in low-grade tumors.

IntroductionProstate cancer (PCa) detection is usually achieved by PSA measurement and, if indicated, further diagnostics. The recent EAU guidelines recommend a first PSA test at the age of 50 years, if no family history of PCa or BRCA2 mutation exists. However, some men might harbor significant PCa at younger age; thus we evaluated the histopathological results of men treated with radical prostatectomy (RP) in their 40 s at our institution.Materials and methodsWe relied on the data of all patients who underwent RP in our institution between 1992 and 2020 and were younger than 50 years at the time of surgery. The histopathological results are descriptively presented. Moreover, we tested the effect of a positive family history on the descriptive results.ResultsOverall, 1225 patients younger than 50 years underwent RP at our institution. Median age was 47 years. Most patients showed favorable histopathological characteristics. However, 20% of patients had extraprostatic disease (≥ pT3a), 15% had ISUP Gleason grade group ≥ 3, and 7% had positive lymph nodes (pN1). Patients with a known positive family history did not have a higher rate of adverse disease as their counterparts with a negative family history.DiscussionOur data show that the majority of patients who were diagnosed with PCa at a very young age had favorable histopathological RP characteristics. However, a non-negligible proportion of patients already showed locally advanced disease and would have probably benefited from earlier PCa detection. This should be kept in mind when PCa screening recommendations are proposed.

Die Ernährungsintervention spielt eine wichtige Rolle im Rahmen der Prähabilitation, einem multimodalen Konzept, das die körperliche Verfassung vor einer Therapie verbessern soll, um Einfluss auf das Outcome der Operation zu erlangen. Im Vordergrund stehen dabei eine Reduktion der postoperativen Komplikationsrate sowie eine Verkürzung der Krankenhausverweildauer und der Rehabilitationsphase. Durch eine individuelle Beratung, die gezielte Substitution von Kalorien, Proteinen und Nahrungsergänzungsmitteln soll der Ernährungszustand optimiert werden. Ein guter Ernährungszustand trägt zur Stärkung des Immunsystems bei und verbessert die Wundheilung. Insbesondere nach Operationen wird die Muskelmasse schnell abgebaut. Durch eine ausreichende Proteinzufuhr, begleitend zu Kraftübungen, kann die Muskulatur bestmöglich erhalten bzw. ein muskulärer Aufbau im Rahmen der Prähabilitation gefördert werden. Trotz der positiven Effekte der Ernährungsinterventionen sind Prähabilitationsprogramme mit Ernährungsinhalten in der Uroonkologie selten und die Evidenz der Programme daher nur unzureichend. Ergebnisse von ersten Studien erscheinen vielversprechend, es sind aber weitere prospektive, randomisierte Studien von hoher Qualität und mit definierten Programminhalten zu den verschiedenen Tumorentitäten notwendig.

γ-glutamyl-hydrolase (GGH) is a ubiquitously-expressed enzyme that regulates intracellular folate metabolism for cell proliferation, DNA synthesis, and repair. Employing GGH immunohistochemistry on a tissue microarray with 12,427 prostate cancers, we found that GGH expression was negative to low in normal prostate epithelium, whereas 88.3% of our 10,562 interpretable cancers showed GGH expression. GGH staining was considered as low intensity in 49.6% and as high intensity in 38.6% of cancers. High GGH expression was linked to the TMPRSS2:ERG-fusion positive subset of cancers (p < 0.0001), advanced pathological tumor stage, and high Gleason grade (p < 0.0001 each). Further analysis revealed that these associations were merely driven by the subset of ERG-negative cancers, High GGH expression was weakly linked to early biochemical recurrence in ERG negative cancers (p < 0.0001) and independent from established histo-pathological parameters. Moreover, GGH expression was linked to features of genetic instability, including presence of recurrent deletions at 3p, 5q, 6q, and 10q (PTEN, p ≤ 0.01 each), as well as to accelerated cell proliferation as measured by Ki67 immunohistochemistry (p < 0.0001). In conclusion, the results of our study identify GGH as an ERG subtype specific molecular marker with modest prognostic relevance, which may have clinical relevance if analyzed in combination with other molecular markers.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.