title: Comparison of tyrosine kinase receptors HER2, EGFR, and VEGFR expression in micropapillary urothelial carcinoma with invasive urothelial carcinoma.
abstract: Invasive micropapillary urothelial carcinomas (MPUC) emerge at higher stages and follow a more aggressive course than conventional invasive urothelial carcinomas (UC). Little is known about the target therapies using tyrosine kinase inhibitors in MPUC. This study is to investigate potential effectiveness of tyrosine kinase receptor inhibitors by determining expression of epidermal growth factor receptor (EGFR), human epidermal receptor 2 (HER2), and vascular endothelial growth factor receptor 2 (VEGFR) proteins in MPUC and UC. 16 cases of MPUC and 16 stage-matched UC were identified. Immunohistochemistry for EGFR, HER2, and VEGFR2 and HER2 gene amplification by fluorescence in situ hybridization (FISH) were performed. HER2 and EGFR proteins were expressed in MPUC and UC, with significantly higher HER2 expression in MPUC (ratio 1.82, p < 0.01). HER2 gene amplification was identified in 4 of 16 MPUC (25 %). Amplification was limited to cases with 3+ HER2 expression (100% concordance). EGFR expression in MPUC was slightly higher than UC but not statistically significant (ratio 1.57, p = 0.19). EGFR and HER2 coexpression was noted in 75% of MPUC and 37.5% of UC. No VEGFR expression was identified in the urothelium. Strong VEGFR expression was noted in stromal vessels in both MPUC and UC. In conclusion, EGFR and HER2 are potential targets for neoadjuvant chemotherapy in MPUC and UC. There is no direct anti-tumor effect expected for VEGFR inhibitors.
authors.affiliation: Department of Pathology and Laboratory Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI, 02903, USA, jli4@lifespan.org.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Li
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Jackson
authors.forename: Dongfang
authors.initials: D
authors.lastname: Yang
authors.forename: Lelia
authors.initials: L
authors.lastname: Noble
authors.forename: Michael
authors.initials: M
authors.lastname: Wheeler
authors.forename: Dolores
authors.initials: D
authors.lastname: MacKenzie
authors.forename: Temitope
authors.initials: T
authors.lastname: Adegun
authors.forename: Ali
authors.initials: A
authors.lastname: Amin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C000588866:KDR protein, human