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From OncoLog, April 2014, Vol. 59, No. 4

Graphic: In Brief

Invasive Bladder Cancer Subtypes Resemble Breast Cancer Subtypes

Researchers have found that the gene expression pattern of muscle-invasive bladder cancer is remarkably similar to that of breast cancer. This resemblance has important implications for treating the most lethal form of bladder cancer.

Scientists at The University of Texas MD Anderson Cancer Center, working with researchers at The University of Texas Graduate School of Biomedical Sciences and other institutions, reported that the gene expression profiles of muscle-invasive bladder cancer fall into three molecular categories that closely resemble three of the four major subtypes of breast cancer.

The researchers analyzed the genetic profiles of 73 flash-frozen muscle-invasive bladder cancer tissue samples from MD Anderson and then validated the initial findings in a set of 57 formalin-fixed, paraffin-embedded muscle-invasive bladder tumor samples, also from MD Anderson. The researchers also performed subtype analyses on muscle-invasive bladder tumor samples collected in clinical trials performed at MD Anderson, Fox Chase Cancer Center, and Thomas Jefferson University Hospital in Philadelphia.

David McConkey, Ph.D., a professor in the Department of Urology, and his colleagues identified a basal subtype of muscle-invasive bladder cancer that is similar to basal (triple-negative) breast cancer; a luminal subtype that is similar to luminal A and B breast cancer subtypes; and a “p53-like” luminal subtype that is also similar to luminal A breast cancer but is characterized by activated wild-type TP53 gene expression.

The basal subtype of muscle-invasive bladder cancer expressed genes that are biomarkers for basal breast cancer (CD44, KRT5, KRT6, and CDH3) and indicate the presence of cancer stem cells and other treatment-resistant features. Like its breast cancer counterpart, the basal bladder cancer subtype was found to be biologically aggressive if left untreated but was sensitive to cisplatin-based chemotherapy. Cisplatin-based chemotherapy followed by cystectomy is the standard of care for muscle-invasive bladder cancer.

The luminal subtype of muscle-invasive bladder cancer expressed gene biomarkers shared by the luminal A and B subtypes of breast cancer (CD24, FOXA1, GATA3, and ERBB2). Luminal bladder cancers were estrogen receptor–positive and had activating mutations in FGFR3, which encodes a growth factor receptor. Drugs that target these receptors may be effective in patients with this bladder cancer subtype.

The p53-like subtype of muscle-invasive bladder cancer was distinguished by its activated wild-type TP53 gene expression signature. The tumors in this category were resistant to cisplatin-based combination chemotherapy. Dr. McConkey said that a recent clinical trial of presurgical chemotherapy for breast cancer found that breast tumors with normal TP53 gene expression signatures also responded poorly to chemotherapy. One explanation for this chemotherapy resistance is that besides promoting cell death, the p53 protein also can simply arrest cell growth and division. Dr. McConkey said, “These dormant cells evade chemotherapy, which preferentially kills dividing cells.”

The report of the study was published in the February edition of Cancer Cell. The researchers are developing streamlined methods for identifying these muscle-invasive bladder cancer subtypes so that the information can be used to guide treatment decisions.

For more information, talk to your physician, visit www.mdanderson.org, or call askMDAnderson at 877-632-6789.

Other articles in OncoLog, April 2014 issue:

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