title: EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides.
abstract: BACKGROUND
  There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder cancer and these methods are therefore not routinely used. Targeting radio-nuclides to the extracellular domain of the receptors is potentially a better possibility.
  
  
  METHODS
  EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose.
  
  
  RESULTS
  EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients.
  
  
  CONCLUSIONS
  At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.
authors: Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors: Jörgen
authors: J
authors: Carlsson
authors: Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors: Kenneth
authors: K
authors: Wester
authors: Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology, Rudbeck Laboratory, Uppsala University Hospital, Uppsala, Sweden.
authors: Manuel
authors: M
authors: De La Torre
authors: Department of Surgical Sciences, Urology, Uppsala University Hospital, Uppsala, Sweden.
authors: Per-Uno
authors: PU
authors: Malmström
authors: Department of Clinical Sciences, General Surgery and Urology, Karolinska Institute at Danderyd Hospital, Stockholm, Sweden.
authors: Truls
authors: T
authors: Gårdmark
keywords: EGFR; HER2; radionuclides; resistance; urinary bladder cancer metastases