Gene Expression Model Predicts Pathological Node Status

A molecular test has been developed that ascertains which bladder cancer patients may have malignant involvement in their lymph nodes at the time of surgery.

A gene expression model (GEM) has been developed that predict the pathological node status in primary tumor tissues. Archival formalin-fixed paraffin embedded (FFPE) tissues can be analyzed by microarray technology to support the model.

A multicenter collaborative study was performed at the University of Colorado Cancer Center, (Aurora, CO, USA), whereby 20 genes were analyzed on specimens from three independent cohorts of patients who underwent cystectomy and lymphadenectomy for bladder cancer. All patients were clinically node negative before cystectomy and had complete pathological staging information. Archival tissues could only be retrieved for 200 of 327 patients reported, of which 185 produced nucleic acid extracts of sufficient quality for microarray analysis.

Tissue core were extracted from the FFPE block and these samples were used for nucleic acid extraction, verification, amplification, and hybridization to HG-U133 plus 2.0 arrays (Affymetrix; Santa Clara, CA, USA), with analysis by robust multichip average (RMA). The investigators broadened the study by identifying ribonucleic acid (RNA) transcripts detected with high fidelity independently of sample preservation, either fresh freezing or FFPE, before development of the GEM. To that end, they used 32 paired fresh frozen and FFPE tissues profiled by microarrays to identify probes which were further refined to ensure they are expressed in transurethral resection (TUR)-acquired tumors as well as cystectomies.

Bladder cancer is the fourth most common cancer diagnosed in males in the USA, who are three times more likely to be diagnosed with the disease than women are. Dan Theodorescu, MD, PhD, urological surgeon, and lead author of the study, said, "Randomized clinical trials have shown that giving neoadjuvant chemotherapy extends patient lives, but only 5% to 15% of patients benefit. Patients who have cancer in the lymph nodes at time of diagnosis are likely to benefit the most. We validated the test's ability to predict lymph node spread of the cancer in a large sample of patients from a randomized trial." A clinical trial of using the test as a treatment guide is being planned. The study was published February 2011, in Lancet Oncology.

Related Links:
University of Colorado Cancer Center
Affymetrix