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Her2 amplification distinguishes a subset of non-muscle-invasive bladder cancers with a high risk of progression
  1. Paul Chih-Hsueh Chen1,
  2. Hui-Jung Yu2,
  3. Yen-Hwa Chang3,
  4. Chin-Chen Pan1
  1. 1Department of Pathology, Taipei Veterans General Hospital & National Yang-Ming University, Taipei, Taiwan
  2. 2Department of Pathology, Cardinal Tien Hospital, New Taipei City, Taiwan
  3. 3Division of Urology, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
  1. Correspondence to Dr Chin-Chen Pan, Department of Pathology, Taipei Veterans General Hospital, No. 201, Shi-Pai Rd, Sec.2, Taipei 11217, Taiwan; ccpan{at}


Background Several studies have employed immunohistochemistry to detect Her2/neu overexpression in urothelial carcinomas, yielding a tremendous range of positive expression rates. Few studies have examined Her2 status in non-muscle invasive bladder cancer (NMIBC) using fluorescence in situ hybridisation (FISH).

Aim To evaluate Her2 amplification in NMIBC (Ta/T1), to correlate the findings with recurrence and progression, and compare the Her2 status between primary and progressive tumours.

Methods FISH and immunohistochemistry for Her2/neu were performed on tissue arrays consisting of 36 papillary urothelial neoplasms of low malignant potential (PUNLMPs), 190 low grade urothelial carcinomas (LG-UCs) and 178 high grade urothelial carcinomas (HG-UCs). 32 cases with specimens of both primary and progressive tumours (from Ta/T1 to T2–4) were included for comparative analyses.

Results 16 HG-UCs (9.0%) showed Her2 gene amplification while none of the PUNLMPs and LG-UCs showed this aberration. There was 100% concordance in the status of Her2 amplification between primary and progressive lesions. Immunohistochemistry and FISH results were in closest agreement when overexpression was defined as 50% of tumour cells showing immunoreactivity. The cumulative incidences of recurrence and progression in Her2-amplified HG-UC were significantly higher than in those without amplification.

Conclusions A subset of high-grade NMIBCs contain Her2 amplification and are associated with markedly aggressive behaviour. Her2 diagnostics are valuable for distinguishing patients who require diligent surveillance and would potentially benefit from anti-Her2 therapies.

  • Histopathology
  • Tumour Markers
  • Urinary Tract Tumours

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