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STAG2 mutation associated with low-risk bladder cancer
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More than one-third of papillary noninvasive bladder cancers harbored STAG2 mutations, according to study results.
Tumors with mutationally inactive STAG2 rarely recurred or progressed, so screening for STAG2 expression may better define treatment and reduce the number of cystoscopies patients undergo, researchers wrote.
“Most bladder cancers are superficial tumors that have not spread to other parts of the body, and can therefore be easily treated and cured. However, a small fraction of these superficial tumors will recur and metastasize, even after treatment,” Todd Waldman, MD, PhD, a cancer geneticist and professor of oncology at Georgetown Lombardi Comprehensive Cancer Center, said in a press release.
The researchers evaluated 2,214 human tumors for STAG2 inactivation.
They determined STAG2 was most frequently inactivated in bladder cancer. Fifty-two (18%) of 295 urothelial bladder cancers evaluated demonstrated complete loss of STAG2 expression. Of tumors with STAG2 inactivation, 36% were low-risk, noninvasive bladder cancers, and 16% were invasive.
Researchers then evaluated a clinically annotated panel of 349 invasive urothelial carcinomas treated with radical cystectomy. Researchers determined STAG2 loss was significantly associated with increased frequency of lymph node metastasis (P=.03). STAG2 loss also was associated with increased risk for disease recurrence (P=.04) and cancer-specific mortality (P=.04).
The discovery has potentially significant clinical applications, according to the researchers.
“A major problem in the treatment of bladder cancer has been the identification of those 15% to 20% of papillary tumors [that] will recur and progress to invasion versus the 80% to 85% [that] will not,” they wrote. “As the immunohistochemical assay for STAG2 loss is robust and routine clinical sequencing of tumors is imminent, the discovery reported here may have near-term implications for the clinical management of patients with bladder cancer.”
Disclosure: The researchers report no relevant financial disclosures.
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