Comparison of Tyrosine Kinase Receptors HER2, EGFR and VEGFR Expression in Micropapillary Urothelial Carcinoma with Invasive Urothelial Carcinoma
Jianhong Li, Dongfang Yang, Lelia Noble, Murray Resnick, Ali Amin. Rhode Island Hospital/Warren Alpert Medical School of Brown University, Providence, RI
Background: Invasive micropapillary urothelial carcinomas (MPUC) emerge at a higher stage and follow a more aggressive course than conventional invasive urothelial carcinomas (UC). Neoadjuvant chemotherapy is recommended as the main adjunct to radical cystectomy for MPUC; therefore identifying an effective regimen is of significant importance. Targeted therapy for UC with tyrosine kinase inhibitors is under investigation, but little is known about the effect of such agents in MPUC. Current study investigats the potential effectiveness for inhibitors of tyrosine kinase receptor by determining their expression.
Design: From 2000 to 2012, 16 cases of MPUC were identified in the archives of Rhode Island Hospital. A control group of 16 UC cases were randomly selected. Immunohistochemistry for antibodies against Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Recptor 2 (Her2) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) was performed on 4mm thick formalin-fixed, paraffin-embedded sections. The staining pattern was semiquantitatively scored and analyzed by two tailed T-Test.
Results: Twelve (75%) of the MPUC patients were male, with mean age of 69.5 years. HER2 and EGFR were expressed in both MPUC and UC. HER2 expression was stronger and more diffuse in MPUC compared to UC (p=0.032). Preliminary data on EGFR showed expression in MPUC; however there was no statistically significant difference of EGFR expression between MPUC and UC. VEGFR, however, did not show any expression in MPUC or UC. In some cases of MPUC and UC, increased angiogenesis was noted that was highlighted by VEGFR.
Conclusions: This is the first study to compare the expression of potential therapeutic targets in MPUC to UC. Increased expression of HER2 and EGFR in MPUC suggests that these molecules can be potential targets for neoadjuvant chemotherapy. VEGFR, however, showed no expression in MPUC or UC. Therefore, despite a potential effect on tumor angiogenesis, VEGFR inhibitors are expected not to have any direct toxic effect on MPUC or UC. Additional studies are required to confirm the findings.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 101, Tuesday Morning