Treatment of muscle-invasive bladder cancer: progress and new challenges.

The management of muscle-invasive bladder cancer has evolved over the last 20 years. Radical surgery, while curative for a significant number of patients, is inadequate for a subgroup with aggressive features including, but not limited to, advanced local stage, lymphovascular invasion on transurethral resection specimen, or variant histology such as small cell carcinoma. It is now clear that chemotherapy can improve the outcome for such patients. Combination platinum-based neoadjuvant chemotherapy is associated with a survival advantage of 5-8% at 5 years over local therapy alone. Improvements in surgical technique are also important and need to be further refined. Biologic-based staging and targeted therapies hold promise for the future. The critical issue in multimodal therapy for this very heterogeneous disease is individualized patient selection. In this review, data are presented with emphasis on the practical application of current knowledge to the management of patients with muscle-invasive bladder cancer.

Evaluation of non-formalin tissue fixation for molecular profiling studies.

Using a general strategy for evaluating clinical tissue specimens, we found that 70% ethanol fixation and paraffin embedding is a useful method for molecular profiling studies. Human prostate and kidney were used as test tissues. The protein content of the samples was analyzed by one-dimensional gel electrophoresis, immunoblot, two-dimensional gel electrophoresis, and layered expression scanning. In each case, the fixed and embedded tissues produced results similar to that obtained from snap-frozen specimens, although the protein quantity was somewhat decreased. Recovery of mRNA was reduced in both quantity and quality in the ethanol-fixed samples, but was superior to that obtained from formalin-fixed samples and sufficient to perform reverse transcription polymerase chain reactions. Recovery of DNA from ethanol-fixed specimens was superior to formalin-fixed samples as determined by one-dimensional gel electrophoresis and polymerase chain reaction. In conclusion, specimens fixed in 70% ethanol and embedded in paraffin produce good histology and permit recovery of DNA, mRNA, and proteins sufficient for several downstream molecular analyses. Complete protocols and additional discussion of relevant issues are available on an accompanying website (http://cgap-mf.nih.gov/).