TY - JOUR
T1 - Immunohistochemistry to enhance prognostic allocation and guide decision-making of patients with advanced urothelial cancer receiving first-line chemotherapy
AU - Necchi, Andrea
AU - Giannatempo, Patrizia
AU - Paolini, Biagio
AU - Lo Vullo, Salvatore
AU - Marongiu, Manuela
AU - Farè, Elena
AU - Raggi, Daniele
AU - Nicolai, Nicola
AU - Piva, Luigi
AU - Catanzaro, Mario
AU - Biasoni, Davide
AU - Torelli, Tullio
AU - Stagni, Silvia
AU - Maffezzini, Massimo
AU - Gianni, Alessandro M.
AU - De Braud, Filippo
AU - Mariani, Luigi
AU - Sonpavde, Guru
AU - Colecchia, Maurizio
AU - Salvioni, Roberto
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Background Knowledge of the expression of molecular drivers and potentially druggable targets might enhance prognostic classification of M UC. Materials and Methods We analyzed archival tissue from patients with UC who underwent first-line chemotherapy for locally advanced (LA) and M disease between the years 2000 and 2013. The following biomarkers were evaluated using IHC: excision repair cross complementation (ERCC) group 1 (ERCC1), epidermal growth factor receptor (EGFR), HER2, VEGFR-3, PDGFRα, p53, and p63. Expression of ERCC1, EGFR, and HER2 was dichotomized as positive (2+, 3+) or negative (≤ 1+). Cox regression models were used to evaluate the association of biomarker expression with progression-free (PFS) and overall survival (OS), after controlling for known prognostic factors. Results Since June of 2009, tissues of 88 cases (27 LA, 61 M) were stained. Rates of positive IHC/number evaluable were as follows: ERCC1: 30 of 66 (45%); HER2: 24 of 52 (46%); EGFR: 31 of 54 (57%); VEGFR-3: 50 of 66 (76%); PDGFRα: 10 of 63 (16%); p53: 25 of 56 (45%); and p63: 46 of 53 (87%). In the multivariable model, PDGFRα was significantly prognostic for poorer PFS (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.01-6.37; P =.047) and trended to significance for poorer OS (HR, 2.66; 95% CI, 0.96-7.42; P =.060) and VEGFR-3 was significantly prognostic for better PFS (HR, 0.33; 95% CI, 0.15-0.74; P =.007) and OS (HR, 0.36; 95% CI, 0.15-0.85; P =.019). The c-index of the model was 0.67 and 0.68 for the 2 end points, respectively. Conclusion Tumor VEGFR-3 and PDGFRα expression appeared to confer a divergent prognostic effect. These data underscore the hurdles in defining the role of angiogenesis as a molecular driver and therapeutic target, and the controversial role of IHC to guide therapeutic decision-making.
AB - Background Knowledge of the expression of molecular drivers and potentially druggable targets might enhance prognostic classification of M UC. Materials and Methods We analyzed archival tissue from patients with UC who underwent first-line chemotherapy for locally advanced (LA) and M disease between the years 2000 and 2013. The following biomarkers were evaluated using IHC: excision repair cross complementation (ERCC) group 1 (ERCC1), epidermal growth factor receptor (EGFR), HER2, VEGFR-3, PDGFRα, p53, and p63. Expression of ERCC1, EGFR, and HER2 was dichotomized as positive (2+, 3+) or negative (≤ 1+). Cox regression models were used to evaluate the association of biomarker expression with progression-free (PFS) and overall survival (OS), after controlling for known prognostic factors. Results Since June of 2009, tissues of 88 cases (27 LA, 61 M) were stained. Rates of positive IHC/number evaluable were as follows: ERCC1: 30 of 66 (45%); HER2: 24 of 52 (46%); EGFR: 31 of 54 (57%); VEGFR-3: 50 of 66 (76%); PDGFRα: 10 of 63 (16%); p53: 25 of 56 (45%); and p63: 46 of 53 (87%). In the multivariable model, PDGFRα was significantly prognostic for poorer PFS (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.01-6.37; P =.047) and trended to significance for poorer OS (HR, 2.66; 95% CI, 0.96-7.42; P =.060) and VEGFR-3 was significantly prognostic for better PFS (HR, 0.33; 95% CI, 0.15-0.74; P =.007) and OS (HR, 0.36; 95% CI, 0.15-0.85; P =.019). The c-index of the model was 0.67 and 0.68 for the 2 end points, respectively. Conclusion Tumor VEGFR-3 and PDGFRα expression appeared to confer a divergent prognostic effect. These data underscore the hurdles in defining the role of angiogenesis as a molecular driver and therapeutic target, and the controversial role of IHC to guide therapeutic decision-making.
KW - Advanced disease
KW - Chemotherapy
KW - Immunohistochemistry
KW - Transitional cell carcinoma
KW - Urothelial cancer
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U2 - 10.1016/j.clgc.2014.08.002
DO - 10.1016/j.clgc.2014.08.002
M3 - Article
C2 - 25193365
AN - SCOPUS:84924350362
VL - 13
SP - 171-177.e1
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
SN - 1558-7673
IS - 2
ER -