Novel approach of human epidermal growth factor receptor 2 detection in noninvasive and invasive transitional cell carcinoma of the bladder.
OBJECTIVE
In recent years over expression of HER2 has been identified in malignant tumors of organs other than breast. Studies of bladder carcinoma that analyzed HER2 protein expression and gene amplification with a variety of nonstandardized methods have shown heterogeneous results. The results reported vary from 2% to 74% of protein over expression, to 4% to 59% of gene amplification of HER2, possibly due to differences in study design, material selection or laboratory methodology.


METHODS
In the present study archival tissue from 87 patients with noninvasive papillary (25) and invasive (62) TCC was analyzed for amplification of the HER2 gene and over expression of its encoded protein. HER2 protein expression was detected by immunohistochemistry using the HercepTest. Routinely processed paraffin embedded tissue was investigated for HER2 gene amplification using CISH and FISH.


RESULTS
Of the invasive 37 (58%) and of the noninvasive 19 (76%) transitional cell carcinomas investigated showed over expression of the HER2 protein (3+ and 2+) using a standardized immunohistochemical method. HER2 gene amplification assays performed on positive cases evaluated by immunohistochemistry were obtained in 81% and 43% of 3+ and 2+ HER2 protein over expressing invasive, respectively, and in 21% of noninvasive papillary bladder tumors. HER2 gene amplification detection results using CISH and FISH showed a concordance of 100%. The occurrence of aneusomy of chromosome 17 in association with HER2 gene amplification was investigated.


CONCLUSIONS
Validation of the HER2 oncogene in bladder cancer may allow for the potential use of Herceptin(R) antibody therapy. Therefore, the appropriate treatment approach has to be based on reliable and standardized analysis. Our results indicate that CISH could provide an accurate and practical alternative to FISH for the clinical diagnosis of HER2 oncogene amplification in bladder cancer.
Hauser-Kronberger
C
C
Department of Pathology, General Hospital and Paracelsus University Salzburg, Salzburg, Austria. c.hauser-kronberger@salk.at
Peham
K
K
Grall
J
J
Rausch
W
W
Hutarew
G
G
Dietze
O
O
D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis*; D006801:Humans; D009361:Neoplasm Invasiveness; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology
D066246:ErbB Receptors