Origin and outcome of metastatic tumours to the testes:a nationwide study

ObjectivesTo perform a retrospective cohort analysis for metastatic tumours in the testes to explore the timing, presentation and prognosis of this particular type of metastases and the factors that influence outcome.Patients and methodsA nationwide retrospective review of pathology reports of patients with pathologically confirmed metastases to the testis between 1991 and 2021 was performed. Data were collected from the Dutch nationwide pathology databank (PALGA) and the Netherlands Cancer Registry. Log-rank testing and Kaplan–Meier analyses were used to assess overall survival (OS), and Cox proportional hazard models were used for multivariate survival analysis.ResultsA total of 175 patients with a testicular metastasis were included. The median (range) age at diagnosis of testicular metastasis was 67 (3–88) years. Testicular metastases originated from a variety of primary tumours, although most frequently from the prostate (40.6%), kidney (13.7%), colon (10.3%), bladder (7.4%) and skin (5.7%). Synchronous testicular metastasis was detected in 53 cases, while 114 metachronous lesions were found after a median (interquartile range) interval of 22 (1–53) months after the original cancer diagnosis. OS after the diagnosis of a testicular metastasis was poor, with a median survival of 14.2 months (95% confidence interval 10.2–18.3). Primary tumour origin was an independent factor for survival, with worst survival for patients with primary skin, bladder and colon cancer.ConclusionTesticular metastases are very uncommon and arise mainly from primary tumours anatomically close to the testes. Most patients develop metachronous testicular metastasis at an oligometastatic disease stage. These metastases are invariably associated with poor survival

Validation of molecular targets in prostate cancer.

Contains fulltext : 48248schalken.pdf (publisher's version ) (Closed access)As prostate cancer is not a single disease, it is important to identify the pivotal pathway in the patient being treated. The molecular environment is the site of current oncological research to define new therapeutic targets for hormone-refractory disease, offering the potential to eventually individualize treatment through stratification of pathways. Targets may be validated either phenotypically (e.g. androgen receptor, cadherin) or functionally (e.g. prostate cancer-specific genes). In addition, several other candidates are potentially suitable, while others await discovery. Important initial steps have been made in the search for prostate cancer stem cells; identifying stem cells and the stromal, hormonal, and other signalling molecules that influence their behaviour would have important implications for managing prostate cancer. Although individual therapeutic pathways might be ineffective in a particular molecular environment, combinations of approaches might be capable of producing synergistic effects. A multimodal approach thus might be the best solution. Determining where best to search for a molecular target, and validating whether the target is associated with a sufficiently aggressive malignant process to justify further study is difficult, but the potential benefits are enormous

Prognostic potential of ERG (ETS-related gene) expression in prostatic adenocarcinoma

PURPOSE: Following patients after prostatectomy can be expensive and stressful, therefore, a novel and reliable approach to improve stratification is needed both at diagnosis of PCa and following its treatment. We evaluate the association of both ERG and claudin-4, claudin-5, and beta-catenin expression in tumor tissues of patients with organ-confined and advanced prostatic adenocarcinomas. METHODS: A total of 30 patients were included in the study. Nine men who underwent radical prostatectomy for organ-confined (pT2N0M0) cancer (OCC), 10 patients with clinically advanced cancer (CAC), and 11 controls with benign prostatic hypertrophy (BPH). Using immunohistochemistry applied to tissue microarrays, each group was evaluated for beta-catenin, claudin-4, claudin-5, and ERG expression. RESULTS: The expression of ERG was higher in the CAC group when compared to OCC and BPH (p = 0.7684, p = 0.0224, respectively). Among these patients, 5 from the CAC (45 %) and 5 from the OCC group (56 %) stained positively for ERG (p = 1.0). The mean staining score for those with ERG+ advanced cancer was greater than that for the ERG+ organ-confined cancer (p = 0.0209). ERG staining correlated with Gleason score (Pearson's correlation: 0.498, p = 0.0051), but not with serum PSA level (Pearson's correlation: 0.404, p = 0.1202). When analyzing outcome data, high ERG expressing tumors have shown a significantly worse overall survival (p = 0.0084). CONCLUSIONS: Our results of presence or absence of claudin-4 and claudin-5 and ERG staining intensities suggest their potential as prognostic factors for prostate cancer

Distinct phenotypes of human prostate cancer cells associate with different adaptation to hypoxia and pro-inflammatory gene expression

Hypoxia and inflammation are strictly interconnected both concurring to prostate cancer progression. Numerous reports highlight the role of tumor cells in the synthesis of pro-inflammatory molecules and show that hypoxia can modulate a number of these genes contributing substantially to the increase of cancer aggressiveness. However, little is known about the importance of the tumor phenotype in this process. The present study explores how different features, including differentiation and aggressiveness, of prostate tumor cell lines impact on the hypoxic remodeling of pro-inflammatory gene expression and malignancy. We performed our studies on three cell lines with increasing metastatic potential: the well differentiated androgen-dependent LNCaP and the less differentiated and androgen-independent DU145 and PC3. We analyzed the effect that hypoxic treatment has on modulating pro-inflammatory gene expression and evaluated the role HIF isoforms and NF-kB play in sustaining this process. DU145 and PC3 cells evidenced a higher normoxic expression and a more complete hypoxic induction of pro-inflammatory molecules compared to the well differentiated LNCaP cell line. The role of HIF1a and NF-kB, the master regulators of hypoxia and inflammation respectively, in sustaining the hypoxic proinflammatory phenotype was different according to cell type. NF-kB was observed to play a main role in DU145 and PC3 cells in which treatment with the NF-kB inhibitor parthenolide was able to counteract both the hypoxic pro-inflammatory shift and HIF1a activation but not in LNCaP cells. Our data highlight that tumor prostate cell phenotype contributes at a different degree and with different mechanisms to the hypoxic pro-inflammatory gene expression related to tumor progression