395 ASSOCIATION OF HER2 STATUS WITH CLINICOPATHOLOGIC OUTCOMES IN MICROPAPILLARY UROTHELIAL CARCINOMA

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You have accessJournal of UrologyUrothelial Cancer: Natural History, Markers & Pathophysiology1 Apr 2013395 ASSOCIATION OF HER2 STATUS WITH CLINICOPATHOLOGIC OUTCOMES IN MICROPAPILLARY UROTHELIAL CARCINOMA Steven Schneider, William Sukov, Igor Frank, Stephen Boorjian, Robert Tarrell, Prabin Thapa, and John Cheville Steven SchneiderSteven Schneider Rochester, MN More articles by this author , William SukovWilliam Sukov Rochester, MN More articles by this author , Igor FrankIgor Frank Rochester, MN More articles by this author , Stephen BoorjianStephen Boorjian Rochester, MN More articles by this author , Robert TarrellRobert Tarrell Rochester, MN More articles by this author , Prabin ThapaPrabin Thapa Rochester, MN More articles by this author , and John ChevilleJohn Cheville Rochester, MN More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1784AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES As HER2 targeted therapies have been successful in the treatment of breast cancer, efforts have been made to identify HER2 abnormalities in other malignancies. Recent studies suggest that HER2 over-expression and/or HER2 amplification may occur commonly in micropapillary urothelial carcinoma (MUC). Given the frequently noted adverse outcomes associated with this histology, identification of novel targets for therapy remains a clinically important topic for investigation. Herein, we evaluated HER2 over-expression and amplification among patients with MUC undergoing radical cystectomy. METHODS We reviewed our institutional registry to identify 61 patients with MUC. Clinical and pathologic features were reviewed and all pathology slides were re-reviewed by a urologic pathologist to confirm micropapillary histology and to evaluate each specimen for HER2 expression using immunohistochemistry (IHC). Specimens were also evaluated for HER2 status by fluorescence in situ hybridization (FISH). HER2 score and HER2 status were determined based on CAP/ASCO guidelines for breast carcinoma. Cancer-specific survival (CSS) was estimated using the Kaplan Meier method and compared with the log-rank test. RESULTS Median postoperative follow-up was 9.6 years (4.0-21.1), during which time 36 patients died from bladder cancer. HER2 expression scores of 0, 1+, 2+, and 3+ on IHC were found in 9 (15%), 21 (34%), 15 (25%), and 16 (26%) specimens, respectively. HER2 amplification was identified by FISH in 9 (15%) tumors, of which 7 were 3+, 1 was 2+ and 1 was 0 by IHC. HER2 status concordance rate was 93% for patients with lymph node positive disease. HER2 status was not associated with gender, age, or pathologic tumor stage at the time of surgery. Patients with HER2 amplified tumors had lower 3-year CSS than patients with non-amplified tumors (13% vs. 55%; p<0.001). Furthermore, an average number of HER2 copies >5.7 or a HER2/Chromosome 17 centromere (CEP17) ratio of >1.12 were likewise associated with decreased CSS on univariate analysis (RR 3.5, p =0.003 and RR 4.2, p<0.001, respectively). CONCLUSIONS HER2 overexpression and HER2 amplification are common in micropapillary urothelial carcinoma and are associated with decreased cancer-specific survival. Pending external validation, HER2 may, therefore, represent a therapeutic target in select patients with this histology. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189 Issue 4S April 2013 Page: e160 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Metrics Author Information Steven Schneider Rochester, MN More articles by this author William Sukov Rochester, MN More articles by this author Igor Frank Rochester, MN More articles by this author Stephen Boorjian Rochester, MN More articles by this author Robert Tarrell Rochester, MN More articles by this author Prabin Thapa Rochester, MN More articles by this author John Cheville Rochester, MN More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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