Prostate cancer (PCa) is one of the major public health problems in Western countries. Recently, the TMPRSS2:ERG gene fusion, which results in the aberrant expression of the transcription factor ERG, ...has been shown to be the most common gene rearrangement in PCa. Previous studies have determined the contributions of this fusion in PCa disease initiation and/or progression in vitro and in vivo. In this study on TMPRSS2:ERG regulation in PCa, we used an androgen receptor and TMPRSS2:ERG fusion double-negative PCa cell model: PC3c. In three cell clones with different TMPRSS2:ERG expression levels, ectopic expression of the fusion resulted in significant induction of cell migration and invasion in a dose-dependent manner. In agreement with this phenotype, high-throughput microarray analysis revealed that a set of genes, functionally associated with cell motility and invasiveness, were deregulated in a dose-dependent manner in TMPRSS2:ERG-expressing cells. Importantly, we identified increased MMP9 (Metalloproteinase 9) and PLXNA2 (Plexin A2) expression in TMPRSS2:ERG-positive PCa samples, and their expression levels were significantly correlated with ERG expression in a PCa cohort. In line with these findings, there was evidence that TMPRSS2:ERG directly and positively regulates MMP9 and PLXNA2 expression in PC3c cells. Moreover, PLXNA2 upregulation contributed to TMPRSS2:ERG-mediated enhancements of PC3c cell migration and invasion. Furthermore, and importantly, PLXNA2 expression was upregulated in metastatic PCa tumors compared with localized primary PCa tumors. This study provides novel insights into the role of the TMPRSS2:ERG fusion in PCa metastasis.
Management of localized prostate cancer (PCa) is a major clinical challenge since most of these cancers would not evolve but a majority of patients will still undergo a life-changing radical surgery. ...Molecular studies have shown that PCa can be classified according to their genomic alterations but none of the published PCa molecular classifications could identify a subtype corresponding to non-evolutive tumours.
Multi-omics molecular profiling was carried out on post-radical prostatectomy material from a cohort of 130 patients with localized PCa. We used unsupervised classification techniques to build a comprehensive classification of prostate tumours based on three molecular levels: DNA copy number, DNA methylation, and mRNA expression. Merged data from our cohort and The Cancer Genome Atlas cohort were used to characterize the resulting tumour subtypes. We measured subtype-associated risks of biochemical relapse using Cox regression models and survival data from five cohorts including the two aforementioned.
We describe three PCa molecular subtypes associated with specific molecular characteristics and different clinical outcomes. Particularly, one subtype was strongly associated with the absence of biochemical recurrence. We validated this finding on 746 samples from 5 distinct cohorts (P=3.41×10−8, N=746 tumour samples), and showed that our subtyping approach outperformed the most popular prognostic molecular signatures to accurately identify a subset of patients with a non-evolutive disease. We provide a set of 36 transcriptomic biomarkers to robustly identify this subtype of non-evolutive cases whose prevalence was estimated to 22% of all localized PCa tumours.
At least 20% of patients with localized PCa can be accurately predicted to have a non-evolutive disease on the basis of their molecular subtype. Those patients should not undergo immediate surgery and rather be placed under active surveillance.
Purpose
To analyse the impact of the presence of extra-target non-clinically significant cancer (NCSC) after high-intensity focused ultrasound (HIFU) hemiablation on oncological results. To analyse ...radical treatment free survival (RTFS) rates at 2–3 years follow-up.
Methods
Retrospective single-centre study of 55 patients treated by primary HIFU hemiablation from 2010 to 2016. Inclusion criteria were unilateral MRI detected CSC, stage ≤ T2b, Gleason score (GS) ≤ 7, at least 6 mm distant from prostate apex. MRI with systematic and targeted biopsies was performed at diagnosis. Follow-up included clinical examination, PSA every 6 month, MRI and biopsies at 1 year and in case of PSA elevation. HIFU retreatment was possible. Whole-gland treatment was indicated in case of positive biopsies with GS ≥ 7 or maximum cancer core length > 5 mm, any GS.
Results
Mean follow-up was 33 months (SD: 17–49 months). Presence or not of an extra-target NCSC in the untreated part of the gland had no impact on RTFS at univariate analysis (
p
= 0.29). 10 (18%) patients had a salvage whole-gland treatment after a median follow-up of 26 months (IQR 17–28). RTFS at 2 and 3 years were 92% and 80%.
Conclusion
Presence or not of an extra-target NCSC in the untreated part of the gland had no impact on RTFS. NCSC lesion can be left untreated and actively monitored. RTFS was 80% at 3 years which support the concept of focal/partial treatment as a treatment option of CSC prostate cancer.
Abstract Objective Desmoid tumours of the head and neck in children are rare, local invasive and potentially fatal tumours. The purpose of this review is to discuss the management of these tumours in ...the light of a case series and a review of the literature. Material and methods This retrospective study summarised the medical data of children treated for desmoid tumours of the head and neck between 1976 and 2014. Results Five of the 6 children were treated by radical surgical resection, with positive surgical margins (R1) in 2 cases, followed by recurrence requiring further resection. One child with a very advanced lesion was treated by weekly methotrexate and vinorelbine chemotherapy for 18 months, allowing 93% reduction of tumour volume without recurrence. Conclusions Desmoid tumours of the head and neck in children are more aggressive than their adult counterparts and are associated with high morbidity and mortality and a high recurrence rate. CT and MRI imaging assessment should preferably be performed before biopsy. External beam radiotherapy must be avoided in children as it is less effective than in adults, and is responsible for long-term cosmetic and functional sequelae and even a risk of second tumours. Treatment is surgical whenever radical resection is possible. In patients presenting an excessive risk of morbidity and mortality, chemotherapy devoid of long-term adverse effects (such as methotrexate in combination with a Vinca alkaloid) can be proposed. Long-term follow-up must be ensured due to the risk of recurrence.
Preoperative assessment of mandibular bone invasion in squamous cell carcinoma of the oral cavity and oropharynx is crucial for optimizing bone resection. The principal aim of this study was to ...evaluate the diagnostic value of CT and MR imaging for the diagnosis of mandibular bone invasion compared to the histological reference. In addition, we assessed the survival impact of bone invasion.
A single-center retrospective study included all consecutive patients treated by mandibular bone interruption for squamous cell carcinoma of the oral cavity and/or oropharynx.
Sixty-eight patients were included. Prevalence of bone invasion on histology was 43%. Sensitivity, specificity and positive and negative predictive value were respectively 70%, 71%, 66% and 76% for CT compared with histologic analysis, 83%, 50%, 59% and 78% for MRI, and 83%, 62% 62%, 83% for associated CT and MRI. The two tests showed good agreement, with kappa index 0.69 (95% CI, 0.49–0.89) (P<0.0001). There was no difference in overall survival (log-rank>0.70) between the groups with and without bone invasion.
CT and MRI are complementary for preoperative assessment of mandibular bone invasion, be it cortical and/or medullary, and in some cases may allow mandibular bone-sparing.
Purpose
To evaluate utility of diffusion-weighted magnetic resonance imaging (DWI) to detect and predict the histological characteristics of upper urinary tract urothelial carcinomas (UTUCs).
...Materials and methods
We retrospectively evaluated 20 suspicious lesions from 19 patients. MRI study included conventional sequences and DWI with apparent diffusion coefficient (ADC) maps calculated between
b
= 0 and
b
= 1,000. ADC values were measured within two different regions of interest (ROI): a small identical ROI placed in the most restrictive part of the tumour and a larger ROI covering two-thirds of the mass surface. The mean ADC values of the tumours were compared with that of normal renal parenchyma using an unpaired Student’s
t
test. Association between ADC values and histological features was tested using non-parametric tests.
Results
Overall, 18 tumours were confirmed histologically as UTUCs. DWI failed to detect two cases of UTUCs (one CIS and one small tumour of 5 mm). There was no statistically significant difference in ADC values measured with the small or large ROI (
p
= 0.134). The mean ADC value of UTUC was significantly lower than that of the normal renal parenchyma (
p
< 0.001). No statistical association was found between ADC values and pathological features (location,
p
= 0.35; grade,
p
= 0.98; muscle-invasive disease,
p
= 0.76 and locally advanced stage,
p
= 0.57).
Conclusion
DWI may be interesting tool for detecting UTUCs regarding the difference of ADC values between the tumours and surrounding healthy tissues. In regard to low frequency of UTUCs, the association of ADC values and histological characteristics need further investigations in a large prospective multi-institutional study.
Steroidogenic factor 1 (encoded by SF1/NR5A1) is a transcription factor with multiple target genes involved in the development and function of multiple steroidogenic and non‐steroidogenic tissues. ...NR5A1 mutations lead to several phenotypes, including sex reversal, spermatogenesis failure, premature ovarian failure and adrenocortical insufficiency. The implication of NR5A1 mutations in spleen development anomalies was recently highlighted. We provide new evidence of this involvement, describing a novel heterozygous non‐sense NR5A1 mutation in a 46,XY‐DSD with polysplenia female proband and her father, who had hypospadias and asplenia.
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