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- Gårdmark, Truls, et al.
(författare)
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Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastases
- 2005
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 95:7, s. 982-986
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the expression of HER2 receptors (previously reported to be over-expressed in malignant urothelium) in both primary tumours and metastases of transitional cell cancer, using two different staining methods and two different scoring techniques, considering the potential use of these receptors as targets for planned systemic anti-HER2 nuclide-based treatment. MATERIALS AND METHODS: HER2 expression was evaluated with two different immunohistochemical methods in 90 patients with primary urinary bladder cancer tumours and corresponding metastases. Sections were first stained with the commercially available breast cancer test kit (HercepTest, Dako, Glostrup, Denmark). Parallel sections were then stained with a modified HercepTest procedure. Two different evaluation criteria were compared; the HercepTest score that requires > or = 10% stained tumour cells (as for breast cancer) and a proposed 'Target score' that requires > 67% stained tumour cells. The latter score is assumed to be preferable for HER2-targeted radionuclide therapy. RESULTS: Using the HercepTest kit, the Target score gave lower fractions of positive primary tumours and metastases than the HercepTest score. The modified HercepTest staining procedure and Target score gave high HER2 values in 80% of primary tumours and 62% of metastases, which is considerably more than that obtained with the HercepTest staining and score. There was a significant decrease in HER2 positivity with increasing distance from the primary tumour. In nine sentinel-node metastases assessed, all but one were HER2-positive. Considering all regional metastases, 74% were positive, and of distant metastases, 47%; 72% of the patients with positive primary tumours also expressed HER2 in their metastases. CONCLUSIONS: When combining the modified HercepTest with customised evaluation criteria, more HER2-positive tumours were diagnosed. The degree of HER2 down-regulation was significantly higher in distant than in regional metastases. HER2-targeted therapy may be an alternative or complementary to other methods in the future treatment of metastatic urinary bladder carcinoma.
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- Gårdmark, Truls, 1965-
(författare)
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Urinary Bladder Carcinoma – Studies of Outcome of Current Management and Experimental Therapy
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis concerns the epidemiology, current and possible future treatment of urothelial cancer of the urinary bladder. The Swedish National Quality Registry for Bladder Cancer 1997-2001 was used to explore epidemiology, current therapies and outcome. More common in men, the incidence for Ta and T1 tumours peaks in the age range 70-79 years. There were differences in treatment activity between the reporting regions. An increasing activity was seen. Older patients received less intravesical treatment, which was also a tendency for women. The five year relative survival for all stages (Ta-T4) was 70%; 93% for Ta and 75% for T1. For Ta or T1 survival did not differ significantly between regions. Because the registry has only been running since 1997 a long term follow-up (ten years) of 250 patients comparing Bacillus Calmette-Guerin and Mitomycin-C, was performed. No differences regarding complementary treatment, progression or survival (overall or disease specific) were shown. Looking for new drugs, gemcitabine was tried for intravesical instillations. Patients were randomised to one of three dose schedules. The effect on a marker tumour lesion was evaluated after nine weeks. The overall complete response rate was 31% (9/29). Side effects were more common in women but generally mild; the most common was nausea. One patient stopped instillations (nausea and fever). No patients were excluded due to pathological changes in laboratory parameters. For metastasised disease, over-expression of the growth factor receptor HER2 on urothelial cancer cells was explored in primary tumours and metastases, aiming at radionuclide target therapy. With a new antigen retrieval procedure and evaluation protocol 80% of primary tumours overexpressed the receptor and 72% remained so in the metastases. In conclusion current therapies were increasingly used by clinicians. Superiority for BCG could not be proven. Prerequisites for new therapies have been explored and the way has been paved for future studies.
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