|dc.description.abstracteng||Background: Bladder cancer causes significant health restrictions and burdens as a common disease, especially among men. The third most common localization for metastases of bladder cancer is the bone which often causes skeletal related events (=SRE). It is necessary to treat the carcinoma itself as well as bone metastases to prevent SRE and protect the patients’ quality of life. The RANK RANKL pathway as a cytokine system used by bone for communication is also abused by different tumour entities to migrate and generate metastases.
Summary of evidence: Healthy bone environment communicates by the cytokine system consisting of RANK, RANKL and OPG. Not only healthy bone uses this pathway but also different cancer entities abuse it for developing metastases. Besides this, several previous studies have shown an expression of these cytokines in different cancer entities itself, e.g. prostate cancer. The objective of this study is to systematically quantify RANK, RANKL and OPG expression in urothelial carcinoma and investigate possible correlation to tumour grading and staging for the first time. Methods: 29 patients with urothelial carcinoma of the urinary bladder were included in this study. At the time of surgery, 13 patients were staged as pTa, 5 as pT2, 4 as pT3 and 7 as pT4 carcinoma. Additionally, 11 biopsies of metastases (lymph node or distant metastases) were examined. 40 specimens were tested for RANK, RANKL and OPG expression by immunohistochemistry, evaluated with the Allred-Score and correlated to the histopathological parameters such as tumour staging and grading.
Results: RANK, RANKL and OPG expression was detected in every urothelial carcinoma specimen. An inverse correlation of the expression of RANKL and staging (p=0,00001 and 0,000006 respectively) as well as grading (p=0,0001) was shown by Kruskal-Wallis and Mann-Whitney U test. An inverse correlation of OPG expression and staging (p=0,0070 and 0,002480 respectively) as well as grading (p=0,0289) was demonstrated. RANK was expressed in all specimens but without any correlation to grading or staging.
Conclusion: Our study demonstrates a RANK-RANKL-OPG pathway expression in urothelial carcinoma for the first time. RANKL and OPG expression show an inverse correlation to staging and grading which is in contradiction to other tumour entities, e.g. prostates cancer. This correlation may be caused by the need of the cytokines for preparation cell migration and metastasis in lower tumour stages. Next experimental steps will be studies on the expression of the cytokines in bone metastases itself as well as studies concerning the correlation of the pathway to clinical parameters such as survival rate, especially in high risk tumours.||de