equine penile squamous cell carcinoma (epScc) is a relatively common cutaneous neoplasm with a poor prognosis. in this study, we aimed to determine the protein expression and colocalisation of FRA1, c-Myc, Cyclin D1, and MMP7 in normal (NT), tumour (T), hyperplastic epidermis and/or squamous papilloma (Hyp/Pap), poorly-differentiated (PDSCC), or well-differentiated (WDSCC) EpSCC using a tissue array approach. further objectives were to correlate protein expression to (i) levels of inflammation, using a convolutional neural network (ii) equine papillomavirus 2 (EcPV2) infection, detected using PCR amplification. We found an increase in expression of FRA1 in EpSCC compared to NT samples. c-Myc expression was higher in Hyp/Pap and WDSCC but not PDSCC whereas MMP7 was reduced in WDSCC compared with NT. There was a significant increase in the global intersection coefficient (GIC) of FRA1 with MMP7, c-Myc, and Cyclin D1 in EpSCC. Conversely, GIC for MMP7 with c-Myc was reduced in EpSCC tissue. Inflammation was positively associated with EcPV2 infection in both NT and EpSCC but not Hyp/Pap. Changes in protein expression could be correlated with EcPV2 for Cyclin D1 and c-Myc. Our results evaluate novel biomarkers of EpSCC and a putative correlation between the expression of biomarkers, EcPV2 infection and inflammation. Equine penile squamous cell carcinoma (EpSCC) is a cutaneous neoplasm with a poor prognosis that often results in euthanasia due to late presentation, treatment difficulties and deterioration. EpSCC are often seen with precancerous pink to yellow plaques and genital papillomas. The lesion is seen mostly at the end of the second and beginning of the third decade of life 1. The term penile intraepithelial neoplasia (PIN) used in humans may also be applied to these lesions. After sarcoids, squamous cell carcinomas are considered the most common equine neoplasm 1-3. Around one tenth of all equine neoplasms are diagnosed in the penis, vulva and ocular adnexa 4,5 of which EpSCC is the most common. Incidence rates of EpSCC, reported more in ponies compared to horses 6 , vary and no specific breed predilection has been ascertained 6. The recorded incidence rates for EpSCCs are between 50-80% of all external genital neoplasms, however one report recorded that EpSCC made up around a fifth of all diagnosed equine cancers in a single UK laboratory over a 29-year period, with the incidence of cutaneous equine tumours also varying by region 6. The possible causes of EpSCC are suggested to be smegma accumulation, ultraviolet light overexposure, chronic irritation and balanoposthitis 7. Chronic inflammation is a known risk factor for cancer development 8. It is also thought that a majority of solid tumours are infiltrated with immune and inflammatory cells 9. The link between human papilloma virus (HPV), cervical cancer 10 and chronic inflammation is known 8. There is evidence to suggest that equine cancers may be initiated, in part, by papillomavirus infection analogous to human cervical and penile cancer 11. These sugge...

Discussion. These results highlight the reality that newborns with exstrophy have significantly reduced compliance and bladder underactivity, which may persist or return to normal values with surgery and age. The primary cause of underactivity is increased connective tissue in relation to detrusor muscle, however detrusor myocyte function remains normal. Finally, the increase of smooth muscle content in the paediatric bladder group indicates a remodelling response of the bladder to surgical correction and time. Excess gestational fibrosis is associated with changed expression of key proteins in the Wnt-signalling pathway, a potential aetiological factor and therapeutic target. Conclusion.Results point to connective tissue deposition as the primary pathological process that determines bladder function with normal myocyte function. Future research that reduces connective tissue deposition may lead to improvement in outcomes for these children.

Neurogenic lower urinary tract (NLUT) dysfunction in paediatric patients can arise after congenital or acquired conditions that affect bladder innervation. With some patients, urinary tract dysfunction remains and is more difficult to treat without understanding the pathophysiology. We measured in vitro detrusor smooth muscle function of samples from such bladders and any association with altered Wnt-signalling pathways that contribute to both foetal development and connective tissue deposition. A comparator group was tissue from children with normally functioning bladders. Nerve-mediated and agonist-induced contractile responses and passive stiffness were measured. Histology measured smooth muscle and connective tissue proportions, and multiplex immunohistochemistry recorded expression of protein targets associated with Wnt-signalling pathways. Detrusor from the NLUT group had reduced contractility and greater stiffness, associated with increased connective tissue content. Immunohistochemistry showed no major changes to Wnt-signalling components except down-regulation of c-Myc, a multifunctional regulator of gene transcription. NLUT is a diverse term for several diagnoses that disrupt bladder innervation. While we cannot speculate about the reasons for these pathophysiological changes, their recognition should guide research to understand their ultimate causes and develop strategies to attenuate and even reverse them. The role of changes to the Wnt-signalling pathways was minor.