Cyclooxygenase‐2 expression on urothelial and inflammatory cells of cystoscopic biopsies and urine cytology as a possible predictive marker for bladder carcinoma

Cyclooxygenase‐2 (COX‐2) is a key inducible enzyme involved in the production of prostaglandins. It contributes to human carcinogenesis by various mechanisms. The aim of the current study was to elucidate the possible involvement of COX‐2 in human bladder carcinoma by examining its expression on both urothelial and inflammatory cells in tissue biopsies and urine cytology samples of different urinary bladder lesions. A total of 65 patients were included in the study and were selected from cases admitted to Urology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt. They represented seven control cases with almost normal‐looking bladder tissue; pure chronic cystitis (n=12); premalignant lesions (18) in the form of squamous metaplasia (n=8) or urothelial dysplasia (n=10) as well as transitional cell carcinoma (TCC) (n=18), and squamous cell carcinoma (SqCC) (n=10). Immunohistochemistry of formalin‐fixed, paraffin‐embedded tissue sections and urine cytology samples was performed for all cases using COX‐2 (H‐62): sc‐7951, a rabbit polyclonal antibody. The study revealed positive COX‐2 expression on the urothelial and inflammatory cells of cystoscopic biopsies from all cases of pure chronic cystitis, squamous metaplasia and SqCC compared with 42.8% and 71.4% of normal controls, respectively. The score of urothelial COX‐2 expression was sequentially up‐regulated from normal to chronic cystitis (either pure or associated with premalignant changes) (p<0.05) to malignant changes (p<0.05). However, the inflammatory cellular expression was down‐regulated with malignant transformation compared with chronic cystitis (p<0.05). In TCC, COX‐2 was over‐expressed on both urothelial and inflammatory cells in advanced tumors. Urine cytology samples were positive for COX‐2 in a comparable manner to that observed in cystoscopic biopsies. Accordingly, the results of the current study have provided new information in two aspects: First, is the possibility of using the differential COX‐2 expression on both inflammatory and urothelial cells as markers for premalignant or malignant transformation; second, besides cystoscopy, urine cytology was found to have a high sensitivity for COX‐2 expression and hence proved to be valuable in malignancy as a non‐invasive substitute for cystoscopy.     

Serotonin content of normal and inflamed appendix: a possible role of serotonin in acute appendicitis

The appendix is lined by a mucosa which has many neuroendocrine cells containing serotonin. Local release of serotonin can act as a mediator of inflammation. In this study we explored the serotonin content of the neuroendocrine cells of the appendixes removed for clinical diagnosis of appendicitis. Appendix specimens were divided into three groups: Acute appendicitis (AA), non‐appendicitis (NA), and follicular hyperplasia (FH). Normal appendix specimens from patients undergoing elective abdominal surgery were used as the control group (NL). All sections were exposed to proteinase K, incubated with anti‐serotonin, chromogranin A, and synaptophysin antibodies, and treated with the LSAB kit. Polygonal cells were seen within the crypt epithelium (enterochromaffin cell, EC) and within the lamina propria (subepithelial neuroendocrine cell, SNC). In AA, only 16 cases (64%) showed serotonin staining in non‐destructed glands. There was a significant reduction in the number of ECs in AA compared to the FH (96%), NA (100%) and NL (100%) groups (P<0.001). Chromogranin and synaptophysin immunostaining also showed a significant reduction in the number of ECs in AA compared with the other three groups (P<0.001). SNC serotonin reactivity was lower in the AA group compared with the other groups (p<0.001). The inflamed appendix is markedly depleted of serotonin in the epithelium and lamina propria. Local serotonin release from ECs and SNCs in the appendix may act as an inflammatory mediator in appendicitis and is likely to be the source of raised blood serotonin in AA.