[Expression of Her2/neu in locally advanced bladder cancer: implication for a molecular targeted therapy].
OBJECTIVE
The Her2/neu oncoprotein, belonging to the erbB-receptor family, is known to contribute to physiological mechanisms of cell proliferation by intrinsic tyrosine-kinase-activity. Overexpression has been shown for several tumors and is known to influence malignant cell proliferation, metastasis and angiogenesis. The clinical use of Her2-targeting agents has emerged in clinical research. In our study, we analyzed Her2/neu expression in urothelial tumors.


METHODS
Her2/neu expression was evaluated immunohistochemically (IHC) in 127 patients undergoing radical cystectomy (DAKO- Herceptest). Additionally, fluorescent-in-situ-hybridisation (FISH) was carried out in all immunohistochemically "2+" cases (n = 41) to assess gene amplification. After grading the Her2/neu-overall status, Her2/neu expression was correlated with clinicopathological parameters and survival data.


RESULTS
An immunohistochemical Her2/neu expression was found in 95 of 127 cases (74.8 %). Of all 41 cases with "2+" staining (32.2 %), 11 cases (26.8 %) showed positive amplification by FISH. Therefore, including the IHC 3+ cases, a Her2/neu overall status of 22 positive (17.3 %) tumors was assessed. Correlation with clinical data showed a relation to lymph node metastasis (P = 0.06), lymph vessel invasion (P = 0.07) and metastasis (P = 0.002). No further associations with other parameters nor with overall survival (P = 0.73) or disease-free survival (P = 0.63) were found.


CONCLUSIONS
Her2/neu upregulation is found in invasive bladder cancer with significant differences in protein expression and gene amplification. The association with lymphogenic and distant metastases implicates a late event in carcinogenesis. Moreover, there was no further association with clinicopathological parameters and survival. The possible role of a molecular targeted therapy of advanced bladder cancer with Her2/neu targeting agents should be assessed in further clinical trials.
Wülfing
C
C
Klinik und Poliklinik für Urologie, Universitätsklinik Münster. wulfing@uni-muenster.de
von Struensee
D
D
Bierer
S
S
Bögemann
M
M
Hertle
L
L
Eltze
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015653:Cystectomy; D003627:Data Interpretation, Statistical; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D016019:Survival Analysis; D013997:Time Factors; D015854:Up-Regulation; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery
D018719:Erb-b2 Receptor Tyrosine Kinases