Cyclooxygenase-2 expression in intraepithelial neoplasia and squamous cell carcinoma of the uterine cervix and its clinicopathological relations

Cyclooxygenase [COX]-2 is involved in the genesis of many tumors; multiple lines of evidence suggested that selective inhibitors of [COX-2] are a novel class of therapeutic and chemopreventive agents for epithelial malignancies. The aim of this study was to investigate the expression of COX-2 in cervical intraepithelial neoplasia [CIN] and squamous cell carcinoma [SCC] of the uterine cervix and its association with Clinicopathological parameters. Twenty one patients with stage I-IV SCC of the cervix, another 21 patients with CIN I-III and 6 patients with histologically normal cervices were included in this study. Patients in the SCC group were treated with radical hysterectomy plus pelvic and para-aortic lymphadenectomy or anterior pelvic exentration. Immunohistochemical study was performed on paraffin embedded tissue sections with COX-2 antibody. Expression of COX-2 was demonstrated in SCC and CIN groups, while it was undetectable in normal cervices. In this study, the prevalence of positive COX-2 expression in SCC group was significantly higher than its prevalence in CIN group [66.7% Vs. 38.1%, p=0.03]. Significantly higher expression of COX-2 was reported in patients with FIGO stage II-IV compared to patients with FIGO stage I [83.3% Vs. 44.4%, p=0.05]. Additionally, patients with parametrial invasion had significantly higher COX-2 expression than patients without [90.0% Vs. 45.5%, p=0.04]. Furthermore, there was significant relationship with respect to COX-2 expression and lymph node involvement [p=0.04]. Regarding the relation between COX-2 expression in both tumor cells and tumor associated tissue eosinophils [TATE], statistically significant inverse relation was reported [p=0.03]. However, the statistical evaluation of COX-2 expression according to age, tumor size, histological type, lymphovascular space invasion [LVSI] and grade of differentiation demonstrated no significant relationship. Our results suggested that, COX-2 expression may have a role in the development and progression of CIN. COX-2 expression is related to most of clinicopathologic and prognostic variables of cervical carcinoma and may be incorporated into the criteria for determination of tumor aggressiveness. The role of COX-2 expression in cancer development and progression makes it a good target for therapy and selective COX-2 inhibitors may be a promising strategy not only for chemoprevention but also for therapeutic approaches in SCC of the uterine cervix

Association between liver fibrosis and glucose intolerance in HCV-infected patients by measuring insulin sensitivity and B-cell function

HCV mainly affects the liver, but also several tissues outside the liver have been reported to be involved, resulting in a wide spectrum of extrahepatic manifestations. Several clinical studies have suggested a possible link between chronic hepatitis caused by hepatitis C [HCV] and the development of diabetes mellitus. We investigated the association between liver fibrosis and glucose intolerance in HCV-infected patients by measuring insulin sensitivity and beta-cell function. Untreated 38 chronic HCV-infected nondiabetic patients were recruited into this study [anti-HCV+]. Eighteen patients with chronic hepatitis other than HCV infection served as the control group [anti-HCV-]. We evaluated insulin sensitivity and beta-cell function of all patients in a fasting state [homeostasis model assessment of insulin resistance [HOMA-R] and homeostasis model assessment of beta-cell function [HOMA-beta]] and after an oral load of 75g glucose [whole -body insulin sensitivity index [WBISI] and delta-insulin/ delta-glucose 30]. For all included patients; histopathological changes in liver biopsies were evaluated. Severe fibrosis was a main factor associated with insulin resistance. There were significant differences in both HOMA-R [P< 0.01] and WBISI [P<0.05] between patients with mild fibrosis [N=17] and those with severe fibrosis [N=21]. Although HOMA-beta was increased significantly in the subjects with severe fibrosis compared with those with mild fibrosis [P<0.05], delta-insulin/ delta-glucose 30 showed no significant difference in stage of liver fibrosis. Last results suggest an uncertain association between liver fibrosis and beta cell function. Our findings suggest that the development of liver fibrosis is associated with insulin resistance in HCV-infected patients

Bcl-2 expression is a cell lineage dependent and p53 independent event in urinary bladder carcinoma

To evaluate the expression of bcl-2 and p53 onco-proteins in normal, hyperplastic, metaplastic, dysplastic and malignant urothelium and their relationship to cell lineage and histopathological parameters. Forty one formalin-fixed and paraffin-embedded blocks were included, thirty six were urinary bladder carcinomas and five cystoscopic normal urinary bladder mucosa. Cases of urinary bladder carcinomas were assessed for grade, stage, nodal metastasis, and presence of hyperplasia, metaplasia, and dysplasia in adjacent mucosa. There were 26 squamous cell carcinoma [SCC], 10 transitional cell carcinoma [TCC], 5 epithelial hyperplasia, 13 squamous metaplasia, 3 glandular metaplasia and 6 focal dysplastic changes. Sections were stained immunohistochemically for the expression of bcl-2 and p53. bcl-2 protein was expressed in basal cells of the normal and hyperplastic urothelium, whereas p53 was not detected. Also bcl-2 was detected in all three cases of glandular metaplasia but p53 was negative. Immunoreactivity for bcl-2 was present in eight of 36 cases [22.2%] [four SCC and four TCC]. Nuclear staining for p53 was observed in sixteen of 36 cases [44.4%] of urinary bladder carcinoma, including 11 of 26 [42.3%] SCC and 5 of 10 [50%] TCC. The expression of bcl-2 and p53 oncoprotein is not correlated with histopathological parameters regarding tumor grade, stage and nodal metastasis in urinary bladder carcinoma. Our results also do not indicate inverse relationship of p53 and bcl-2 immunoreactivity. We suggested that bcl-2 expression was cell lineage dependent as evident by [100%] positively in glandular metaplasia and two foci of adenocarcinoma and significantly high prevalence in TCC [40%] than SCC [15.4%]