Parathyroid hormone receptor 1 (PTHR1) is a prognostic indicator in canine osteosarcoma

Osteosarcoma (OS) is the most common malignant primary bone tumour in humans and dogs. Several studies have established the vital role of parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) in bone formation and remodeling. In addition, these molecules play a role in the progression and metastasis of many human tumour types. This study investigated the expression of PTHR1 and PTHrP in canine OS tissues and assessed their prognostic value. Formalin-fixed, paraffin-embedded tissue samples from 50 dogs diagnosed with primary OS were immunolabeled with antibodies specific for PTHR1 and PTHrP. The immunostaining intensity of tumours from patients with OS was correlated with survival time. Both PTHR1 and PTHrP were detected in all OS samples (n = 50). Dogs with OS tumours showing high immunostaining intensity for PTHR1 (n = 36) had significantly shorter survival times (p = 0.028, Log Rank; p = 0.04, Cox regression) when compared with OS that had low immunostaining intensity for PTHR1 (n = 14).PTHrP immunostaining intensity did not correlate with survival time (p > 0.05). The results of this study indicate that increased expression of PTHR1 antigen in canine OS is associated with poor prognosis. This suggests that PTHR1 may be useful as a prognostic indicator in canine OS

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Fibroblastic subtype has a favourable prognosis in appendicular osteosarcoma of dogs

Osteosarcoma (OS) is an aggressive malignant bone neoplasm that occurs mostly in the appendicular skeleton of dogs and people. OS is classified based on the presence of malignant stroma and the formation of extracellular matrix into osteoblastic, chondroblastic and fibroblastic forms. This study investigated the correlation between the three histological subtypes of canine OS and clinical outcome. Additionally, we examined whether there was any difference in the immunolabelling of desmin, S100 and neuron-specific enolase (NSE) between the three histological subtypes. Formalin-fixed and paraffin wax-embedded tissues from 87 dogs with primary OS were available for this study. The survival times were correlated with appendicular OS subtypes in dogs that were treated surgically, received adjuvant chemotherapy and had no pulmonary metastasis at the time of diagnosis. Dogs with an appendicular fibroblastic OS had significantly prolonged mean average survival times (546 105 days) in comparison with dogs having appendicular osteoblastic (257 48 days) or appendicular chondroblastic (170 28 days) OS (P ¼ 0.003, Log Rank). The results also revealed that the appendicular chondroblastic subtype is a significant indicator for poor prognosis in dogs compared with the fibroblastic or osteoblastic subtypes (P ¼ 0.006, Cox regression). Moreover, the findings indicated that there was no significant correlation between the localization of desmin, NSE or S100 and histological subtypes. Importantly, dogs with appendicular fibroblastic OS were found to have a better prognosis when compared with dogs with other subtypes. This may suggest that histological subtypes of appendicular OS have diverse behaviour and could be used to categorize patients for risk-based assessment

Appendix Table 1:

Owner response scores and their description.</p

Appendix Table 2:

All cases of feline antebrachial fractures, includes configuration, complications, and final outcomes.</p

Multiple loci on 8q24 associated with prostate cancer susceptibility

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33)