Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder
NEUROUROLOGY AND URODYNAMICS
Authors: Firouzmand, Sepinoud; Ajori, Ladan; Towse, Jonathan; Allameh, Farzad; Najafi, Saman; Javed, Saqib; John, Babbin; Langley, Stephen E. M.; Fry, Christopher H.; Young, John S.
Abstract
Aim To characterize purinergic signaling in overactive bladder (OAB). Methods Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n = 12) and Western blot analysis (n = 28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid-stream urine sample. Bioluminescent assays were used to quantify adenosine triphosphate (ATP; n = 66) and adenosine diphosphate (ADP; n = 60) concentrations, which were normalized to creatinine (Cr) concentration. All participants completed a questionnaire (International Consultation on Incontinence Questionnaire - Overactive Bladder) to score urinary symptoms of OAB. Results P2Y6 immunoreactivity, more prominent in the urothelium (colocalized with the uroepithelial marker pan-cytokeratin), was more greatly expressed in OAB compared to age- and sex-matched controls (benign prostatic hyperplasia) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (P = .009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (P = .010 and P = .042, respectively). Conclusions The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signaling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.
Desmoplastic Small Round Cell Tumor of Parotid Gland: A Rare Entity With Diagnostic Challenge
INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY
Authors: Cai, Zhenjian; Zhang, Lin; Karni, Ron J.; Saluja, Karan; Liu, Jing; Zhu, Hui
Abstract
Desmoplastic small round cell tumor (DSRCT) is a rare malignant mesenchymal neoplasm that typically affects young patients and presents as large intraabdominal masses. We report a rare case of parotid gland DSRCT in a 38-year-old man. The tumor cells were large sized and form irregular nests embedded in abundant desmoplastic stroma. Immunohistochemically, the tumor cells were positive for cytokeratin, GATA3, p40, and p63. Working differential diagnosis included squamous cell carcinoma, myoepithelial carcinoma, hyalinizing clear cell carcinoma, NUT (nuclear protein of the testis) carcinoma, and adamantinoma-like Ewing sarcoma. The characteristic morphologic features and presence of EWSR1-WT1 gene fusion are diagnostic of DSRCT. Salivary gland DSRCT is an exceedingly rare entity, with only 6 cases reported in the literature.