gms | German Medical Science

Introduction: Mxi-2 is the truncated variant of MAPK p38. The expression of Mxi-2 is associated with renal cell carcinoma and prostate cancer. Vimentin3 (Vim3) is the truncated variant of vimentin. The expression of Vim3 is already associated with prostate cancer in serum and allows the identification of renal oncocytoma. Until now, there is no proper diagnostic tool, which allows the differenation between noninvasive and invasive bladder cancer, and the therapy response after neoadjuvant chemotherapy.

Material and Methods: The expression of Mxi-2 and Vim3 were determined in bladder tissue samples from 10 healthy controls and 30 bladder cancer in different tumor stages via immunofluorescence. Furthermore, an IHC for Mxi-2 was established. In addition, urine from healthy controls (n=20) and bladder cancer (n=100) patients with different tumor stages were tested for the expression of Mxi-2 and Vim3 via ELISA. For external validation, additional 100 urine samples were provided by the department of Urology in Bad Sarrow.

Results: The determination of Mxi-2 and Vim3 in urine allows the differenation between Non-Muscle Invasive (NMIBC) and Muscle Invasive Bladder Cancer (MIBC). Here, a significant difference between NMIBC pTa and pT1 tumor and MIBC (pT2-–T4) was detected. For Mxi-2 a sensitivity of 92% and specificity of 88% and for Vim3 a sensitivity of 82% and specificity of 84% were determined in the patient cohort of Cologne. In an independent validation cohort Mxi-2 determination reached a sensitivity of 80% while Vim3 reached a specificity of 80% and a sensitivity of 72%.

Conclusions: The determination of Mxi-2 and Vim3 in urine allows a quick and inexpensive differenation between NMIBC and MIBC with a high diagnostic accuracy for tailored surgical and therapeutic evaluation. Comparison of Mxi-2 and Vim3 with existing urine test systems for bladder cancer such as NMP22, BTA stat and Uromonitor are ongoing. Prospective validation of the urine-based prediction of muscle invasiveness in ongoing in the prospective, multicenter Bladder BRIDGister. Moreover, biomarker results will be compared with multiparametric MRI to establish an integrated, non-invasive platform for robust MIBC classification before surgery.