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.
Objective: to assess expression of p27 and survivin in chronic gastritis with/without H. pylori ± intestinal metaplasia (IM) and in intestinal-type gastric cancer (IGC). Materials and Methods: Immunohistochemical staining for p27 and survivin on paraffin-embedded sections of 20 chronic gastritis, 20 H. pylori gastritis, 15 H. pylori gastritis with IM, 50 IGC, and 10 controls. Positivity (number of positive cases) and expression (mean percentage of positive gastric cells) for both proteins were evaluated. Results: P27 positivity and expression decreased from control to chronic gastritis to H. pylori gastritis to H. pylori gastritis with IM. In IGC, p27 positivity and expression were lower than controls and chronic gastritis but higher than H. pylori gastritis ±IM. High grade and advanced stage IGCs have insignificantly lower p27 positivity and expression than low grade and early stage IGCs. By contrast, survivin positivity and expression increased from chronic gastritis to H. pylori gastritis to H. pylori gastritis with IM to IGCs. High grade and advanced stage IGCs have significantly higher survivin positivity and expression than low grade and early stage IGCs. Males have higher positivity and expression for p27 and survivin than females. Conclusion: Inverse relation between p27 and survivin in H. pylori gastritis, H. pylori gastritis with IM and IGCs lesions, suggesting that both proteins could be used as potential prognostic and/or diagnostic biomarkers in H. pylori and IM associated-gastritis as well as in IGC.
Background:Prostate cancer (PCa) is a common health problem in elderly. RAGE (Receptor for advanced glycation end products) is overexpressed in multiple human cancers. SOX2 (Sex-determining region Y box 2) also functions as an oncoprotein and promotes cancer progression but the mechanisms involved remain largely unknown. Aim:The current study investigated the expression patterns of RAGE and SOX2 in benign and malignant prostate samples in correlation with the histopathological findings in order to evaluate their role as prognostic markers or therapeutic targets. Methods:Immunohistochemical staining for RAGE and SOX2 antibodies was applied on 87 prostatic biopsies [16 of prostatitis, 20 of benign prostatic hyperplasia (BPH) and 51 of PCa]. Results:Expression of RAGE and SOX2 (percentage of positive cells) was significantly higher in PCa lesions compared with prostatitis (p<0.01) and BPH (p<0.0001) and was also significantly higher in prostatitis compared with BPH lesions (p<0.01). Also, percentage of positive RAGE and SOX2 cells showed a significant stepwise increase from Gleason Grade 3 to Grade 5 and were significantly higher in high Gleason Scores (≥8) compared to lower Scores (≤7) with statistical significance (p=0.001). Conclusion:RAGE and SOX2 were up-regulated in prostate cancer lesions, mainly in advanced grades, suggesting an active role of both antigens in the development and progression of prostate cancer and expecting the possibility of their use as therapeutic targets.
BACKGROUND: Worldwide gastric cancer (GC) ranks sixth in incidence and second in mortality among all malignancies. CDX2 has an essential role in the development and maintenance of intestinal differentiation in the gut and ectopic sites such as intestinal metaplasia (IM) of the stomach. SOX2 contributes to the cell lineages normally found in the stomach, suggesting contribution in gastric differentiation. AIM: The aim of the study was to assess the expression of CDX2 and SOX2 in chronic gastritis (CG) lesions associated with Helicobacter pylori, IM, or dysplasia as well as in intestinal-type GC. METHODS: Immunohistochemical staining for CDX2 and SOX2 were applied on archival paraffin blocks from 80 CG cases, 40 intestinal-type GC cases, and 10 controls. CG cases were either of non-specific inflammation or associated with H. pylori infection. GC cases were of intestinal-type only, excluding any other type of GC. Control cases were of minimal gastritis, negative for H. pylori, IM, and dysplasia. RESULTS: CDX2 expression was correlated with CG associated with H. pylori, IM, and dysplasia as well as with more differentiated and less invasive pattern of intestinal-type GC, while SOX2 expression was correlated with CG negative for H. pylori and IM as well as with less differentiated and more invasive intestinal-type GC. CONCLUSION: Both CDX2 and SOX2 could predict the behavior of CG disease over time and plan the suitable line of treatment and both proteins could be potential targets for novel therapeutic interventions.
Background Bladder cancer (BC) is the tenth most common cancer worldwide with urothelial carcinoma (UC) being the main histologic subtype. Survivin is an apoptosis inhibitor that is associated with tumor proliferation and invasion. P27 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation. The expression of both proteins was variable among different solid tumors including UC. Methods We aimed to investigate the expression of survivin and P27 in UC of urinary bladder and correlate their expressions with histopathological parameters in an attempt at studying the possibility of their use as targeted therapies. The investigation was performed through immunohistochemical staining for both proteins on sections belonging to 60 UCs and 12 mild chronic cystitis cases (controls). Immunopositivity (number of positive cases) and expression score (percentage of positive urothelial cells) were evaluated. Results Both survivin and P27 were absent in urothelial cells of mild chronic cystitis lesions while expressed in 60% and 43.3% of UCs, respectively. High score of survivin and low score of P27 were associated with poor prognostic factors of UC (solid pattern, high grade, and deep tumors). By logistic regression test, survivin expression can be a predictive risk factor associated with solid pattern and high-grade UC, while P27 expression can be a predictive risk factor associated low-grade UC. Conclusion High survivin and low P27 expression scores were associated with the studied prognostic factors of UC. Both proteins may play a role in UC progression and can have a value as prognostic and/or diagnostic markers of UC, as well as targeted therapies.
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