Immunohistochemical Expression of Vitamin D Receptor in Uterine Fibroids.

One of the many factors involved in the development of uterine fibroids is vitamin D deficiency. One aspect of this deficiency is decreased serum concentration of calcidiol-25(OH)D, a metabolite of D3 vitamin. The active form of vitamin D3, which arises after numerous enzymatic reactions, is calcitriol-1,25(OH)2D3; this compound is transported to various body tissues. Vitamin D possesses extra-genomic effects due to its influence on various signaling pathways, i.e., through activating tyrosine kinases and by genomic effects via binding to a specific nuclear receptor, vitamin D receptor (VDR). The vitamin D/VDR complex regulates the expression of genes and is involved in the pathogenesis of fibroids. Numerous studies have shown that vitamin D supplementation reduces fibroid size. It has also been shown that the expression of VDR in myoma tissue is significantly lower than in the uterine muscle tissue at the tumor periphery. However, the expression of VDR in non-myoma uterine muscle has not previously been investigated. Our VDR expression studies were performed immunohistochemically with tissue microarrays (TMA) in three tissue groups: 98 uterine myoma tissues, 98 uterine tissues (tumor margin), and 12 tissues of normal uterine muscle (i.e., without fibroids). A statistical analysis showed significantly lower VDR expression in uterine muscle at the periphery of the fibroid than in healthy uterine muscle. Lower expression of VDR at the periphery of the myoma compared to that in normal uterine muscle may indicate potential for new myomas. This observation and the described reduction in the size of fibroids after vitamin D supplementation supports the hypothesis of causal development of uterine fibroids and may be useful for the prevention of re-development in the event of their excision from the uterus.

The Participation of p53 and bcl-2 Proteins in Gastric Carcinomas Associated with Helicobacterpylori and/or Epstein-Barr Virus (EBV).

In the presented studies p53 and bcl-2 proteins expression were evaluated in samples of gastric carcinomas in patients with Helicobacter pylori or EBV or without H. pylori/EBV infection. The studies were conducted on 64 adult patients with gastric adenocarcinomas: 16 patients with H. pylori (cagA+)-positivity (group 1), 14 with EBV-positive tumours (group 2), 12 with H. pylori/EBV-positive tumours (group 3) and 22 patients with H. pylori/EBV-negative tumours (group 4). H. pylori presence in gastric tumour specimens was detected using Giemsa staining and bacterial culture technique. Moreover, cagA gene was detected using PCR. EBV infection was detected based on EBER presence in the tissue by RNA in situ hybridization. Expressions of p53 and bcl-2 proteins were analysed using immunohistochemistry. Expression of p53 was noted in 14 (84%) patients from group 1, 8 (57%) patients from group 2, 7 (58%) patients from group 3, and 19 (86%) patients from group 4, whereas expression of bcl-2 was noted in 12 (75%) patients from group 1, in 10 (71%) patients from group 2, 9 (75%) patients from group 3, and 6 (27%) patients from group 4. The obtained results allow the conclusion, that H. pylori (cagA+)-associated development of the gastric adenocarcinoma is determined by abnormalities in the p53 protein function and overexpression of anti-apoptotic bcl-2 protein, whereas EBV-associated adenocarcinomas seem to be related with apoptosis resistance associated with bcl-2 overexpression.

Large bowel mucosal neoplasia in the original specimen may increase the risk of ileal pouch neoplasia in patients following restorative proctocolectomy for ulcerative colitis.

PURPOSE: Restorative proctocolectomy is a current gold standard procedure for patients who require a colectomy for ulcerative colitis. The incidence of ileal pouch neoplasia is low. The aims of this study were to assess the prevalence of neoplasia in ileal pouch and investigate the risk factors for ileal pouch neoplasia. METHODS: A total of 276 patients who underwent restorative proctocolectomy for ulcerative colitis between 1984 and 2009 were analyzed. Results of histological examinations of both original specimen and biopsies from the J-pouch taken during routine pouch endoscopy were evaluated. Patients' records were analyzed for ulcerative colitis duration, the time from pouch creation to pouch neoplasia, presence of pouchitis, as well as the concurrent primary sclerosing cholangitis. RESULTS: Analyzing the original specimen of large bowel, fifty-six lesions of low-grade dysplasia, twenty-five high-grade dysplasia, and five adenocarcinoma were revealed. All patients with dysplasia (n = 8) or adenocarcinoma (n = 1) of the J-pouch were positive for dysplasia in the original specimen. Duration of ulcerative colitis before surgery and duration time following restorative proctocolectomy were found as risk factors for J-pouch neoplasia with a significant difference (p = 0.01 and p = 0.0003, respectively). Patients with pouch neoplasia developed significantly more severe pouchitis (p = 0.00001). CONCLUSIONS: Neoplasia of the J-pouch is rare. Patients with neoplasia in the original specimen are more susceptible to develop neoplasia in the J-pouch. Precise follow-up in patients with neoplasia lesions in the original specimen should be recommended. Moreover, in patients with risk factors, the exact surveillance pouch endoscopy should be recommended.