The prostanoid thromboxane (TX) A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.

Umbilical artery thrombosis is a rare occurrence and is associated with poor neonatal outcomes. We present a series of 7 cases occurring over a 13-year period. The National Maternity Hospital is a tertiary referral center with approximately 10,000 births per annum. Cases were identified by a keyword search on the laboratory computer system. Seven cases were retrieved over a 13-year period (from an estimated 116,000 births): 5 cases from 7306 placentas and 2 cases from 1174 autopsies performed. Only cases with isolated umbilical artery thrombosis were included in the study. Placental histology from all cases was examined, placental gross findings were recorded, and clinical information and Doppler findings were obtained. Two infants were stillborn, and an additional 3 of the 7 cases were small for dates. All liveborn infants had a complicated neonatal course: 1 infant had a caudate infarction, 1 was born with partial acrania and schizencephaly, and 1 had a prolonged intensive care unit admission for low birth weight and jaundice. One case had absent end diastolic flow on Doppler ultrasound. Three cases had a cord diameter narrower than that expected for gestational age. All cases showed evidence of placental hypoperfusion. Umbilical artery thrombosis is a rare occurrence and carries a poor prognosis.

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Introduction: Penile cancer is a rare malignancy, with a European-wide annual incidence rate of 1/100 000 males. Approximately one-third of cases are attributable to human papillomavirus (HPV) infection. p16INK4a is a recognized surrogate marker for HPV infection in penile cancer. University Hospital Waterford (UHW) is the national referral center for penile cancer in Ireland. We report the prevalence of HPV infection and histological characteristics of an Irish penile cancer cohort using p16INK4a as a surrogate marker. Methods: Patients who attended UHW for penile cancer surgery between June 2015 and November 2020 were entered into a prospectively maintained database. Clinical, histopathological, and outcome data were collected. Results: Over the study period, 70 patients with a histological diagnosis of penile squamous cell carcinoma had staining for p16INK4a, of whom 64% were positive. p16INK4a positive patients were significantly younger at diagnosis, with a mean age of 61±15 years compared to 68±12 (p <0.05). Of note, 97% of tumors with high-risk histology were p16INK4a positive (p<0.001). p16INK4a positivity was more prevalent among higher-grade tumors (p<0.02). Interestingly, p16INK4a status was not associated with recurrence-free or overall survival. Conclusions: Our data is representative of the Irish landscape in penile cancer over the last five years. Using p16INK4a staining, we demonstrate a high rate of HPV prevalence in penile cancer cases in our patient cohort, which is associated with prognostically worse tumor subtypes. This would suggest that HPV vaccination of adolescent boys is a useful public health intervention in preventing penile cancer in the Irish male population.