Amplification of HER2 has been found in micropapillary urothelial carcinoma (MPUC), according to a study online ahead of print in Modern Pathology (doi:10.1038/modpathol.2013.201).The data also show that, as with breast cancer, HER2 amplification in MPUC results in a faster-growing form of cancer that spreads quickly and has a higher chance of recurrence.
“Trastuzumab is effective in patients with HER2-amplified breast cancer, and recent studies indicate that the drug is effective against upper gastrointestinal tract cancers that also exhibit HER2 amplification, suggesting that effectiveness is not limited only to breast cancer,” the study's lead author John Cheville, MD, a pathologist at Mayo Clinic, explained in an email. “Therefore, our studies suggest that HER2 may be a target in MPUC.”
The researchers reviewed tissue slides of the 61 patients with micropapillary urothelial carcinoma in the Mayo Clinic Cystectomy Registry who had undergone radical cystectomy between 1980 and 2008, as well as 100 cases of urothelial carcinoma matched for stage, age of patient, ECOG status, receipt of perioperative chemotherapy, and the decade of surgery.
HER2 amplification was identified in 15 percent of the MPUC cases compared with nine percent of the typical urothelial carcinomas. No heterogeneity of HER2 amplification was identified. None of the patients with MPUC and HER2 amplification survived for five years, versus 40 percent of the patients with MPUC without HER2 amplification.
In addition, HER2 amplification was associated with a nearly threefold increased risk of death from bladder cancer.
One of the limitations of the study was that it was retrospective and non-randomized, the researchers noted—and the findings require validation through either a large, multi-institutional retrospective study or preferably through a prospective clinical trial examining the prognostic significance of HER2 amplification and the application of targeted therapy in the setting of cystectomy.
For ongoing trials in bladder cancer patients it will be important to review patients' pathologies, Cheville also noted. “These findings show that it is critical for pathologists to recognize this type of bladder cancer and that providers order the appropriate tests. This will be essential for any clinical trial examining the effectiveness of trastuzumab in treating MPUC.”