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.
information, talk to your physician, visit www.mdanderson.org, or call askMDAnderson at 877-632-6789.
articles in OncoLog, April 2014 issue:
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