Insulin-like growth factor-1 receptor overexpression is associated with outcome in invasive urothelial carcinoma of urinary bladder: a retrospective study of patients treated using radical cystectomy.
OBJECTIVE
To assess the insulin-like growth factor-1 receptor (IGF1R) expression in urothelial carcinoma (UC) and its prognostic role in relation to clinicopathologic parameters.


METHODS
A total of 100 cases of invasive UC were evaluated using tissue microarrays. Membranous IGF1R staining was evaluated using immunohistochemistry. A scoring method analogous to that of HER2 expression in breast carcinoma was used, and the highest score was assigned in each tumor. IGF1R was considered overexpressed in cases with score≥1.


RESULTS
We found IGF1R overexpression in 62% of invasive UC. IGF1R overexpression was associated with race (P=.04) and pT category (P=.03). Median follow-up was 29 months (range, 0.5-212). Progression rate was 60%, and overall mortality and cancer-specific mortality rates were 69% and 51%, respectively. In invasive UC, IGF1R overexpression was significantly associated with overall mortality and cancer-specific mortality (Mantel Cox P=.0002 and P=.006, respectively). IGF1R overexpression was associated with increased hazard ratios (HRs) for overall mortality (HR=2.63, P=.001) and cancer-specific mortality (HR=2.45, P=.01), independently and after adjusting for clinicopathologic features and treatment modalities.


CONCLUSIONS
We found IGF1R overexpression in 62% of bladder UC. More importantly, IGF1R overexpression was a significant predictor of overall mortality and cancer-specific mortality, suggesting its potential role as a prognosticator in UC of bladder.
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
Nilda
N
Gonzalez-Roibon
Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD.
Jenny J
JJ
Kim
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
Sheila F
SF
Faraj
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD; Office of Scientific Research, Norte University, Asunción, Paraguay.
Alcides
A
Chaux
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
Stephania M
SM
Bezerra
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
Enrico
E
Munari
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
Carla
C
Ellis
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
Rajni
R
Sharma
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD.
Daniel
D
Keizman
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD.
Trinity J
TJ
Bivalacqua
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD.
Mark
M
Schoenberg
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD.
Mario
M
Eisenberger
Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD.
Michael
M
Carducci
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD. Electronic address: gnetto1@jhmi.edu.
George J
GJ
Netto
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001707:Biopsy, Needle; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality* / Q000601:surgery*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery
D014408:Biomarkers, Tumor; D017526:Receptor, IGF Type 1