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Erschienen in: World Journal of Urology 2/2017

07.06.2016 | Original Article

HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC)

verfasst von: Francesco Soria, Marco Moschini, Andrea Haitel, Gregory J. Wirth, Jose A. Karam, Christopher G. Wood, Morgan Rouprêt, Vitaly Margulis, Pierre I. Karakiewicz, Alberto Briganti, Jay D. Raman, Solene-Florence Kammerer-Jacquet, Romain Mathieu, Karim Bensalah, Yair Lotan, Mehmet Özsoy, Mesut Remzi, Kilian M. Gust, Shahrokh F. Shariat

Erschienen in: World Journal of Urology | Ausgabe 2/2017

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Abstract

Purpose

The aim of our study was to evaluate the expression pattern of HER2 overexpression in patients with upper tract urothelial carcinoma (UTUC) and to evaluate its association with clinical outcomes.

Methods

This multicenter retrospective study included 732 patients treated with radical nephroureterectomy for UTUC. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest: Scores of 0 or 1 were considered negative and 2 or 3 as positive. To qualify for 2 scoring, complete membrane staining of more than 10 % of tumor cells at a moderate intensity had to be observed.

Results

HER2 was overexpressed in 262 (35.8 %) patients. It was associated with pathologic characteristics such as more advanced T stage (p < 0.001), presence of lymph node metastasis (p = 0.006), high-grade tumor (p < 0.001), tumor necrosis (p = 0.01) and lymphovascular invasion (p = 0.02). Patients with HER2 overexpression had a 1.66-fold increased risk of experiencing disease recurrence (95 % CI 1.24–2.24, p = 0.001), 1.55-fold increased risk of death (95 % CI 1.21–1.99, p = 0.001) and 1.81-fold increased risk of cancer-specific death (95 % CI 1.33–2.48, p < 0.001). On multivariable analysis that adjusted for the effects of standard clinicopathologic variables, HER2 overexpression remained associated with disease recurrence (p = 0.04), overall (p = 0.02) and cancer-specific mortality (p = 0.02).

Conclusions

Approximately, one-third of UTUC patients overexpressed HER2. HER2 overexpression was associated with features of clinically and biologically aggressive disease as well as prognosis. HER2 may represent a good marker for therapeutic risk stratification and potentially a target for therapy in some UTUC tumors.
Literatur
4.
Zurück zum Zitat Margulis V, Shariat SF, Matin SF, Kamat AM, Zigeuner R, Kikuchi E et al (2009) Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. Cancer 115:1224–1233. doi:10.1002/cncr.24135 CrossRefPubMed Margulis V, Shariat SF, Matin SF, Kamat AM, Zigeuner R, Kikuchi E et al (2009) Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. Cancer 115:1224–1233. doi:10.​1002/​cncr.​24135 CrossRefPubMed
6.
Zurück zum Zitat Rouprêt M, Hupertan V, Seisen T, Colin P, Xylinas E, Yates DR et al (2013) Prediction of cancer specific survival after radical nephroureterectomy for upper tract urothelial carcinoma: development of an optimized postoperative nomogram using decision curve analysis. J Urol 189:1662–1669. doi:10.1016/j.juro.2012.10.057 CrossRefPubMed Rouprêt M, Hupertan V, Seisen T, Colin P, Xylinas E, Yates DR et al (2013) Prediction of cancer specific survival after radical nephroureterectomy for upper tract urothelial carcinoma: development of an optimized postoperative nomogram using decision curve analysis. J Urol 189:1662–1669. doi:10.​1016/​j.​juro.​2012.​10.​057 CrossRefPubMed
7.
Zurück zum Zitat Jeldres C, Sun M, Lughezzani G, Isbarn H, Shariat SF, Widmer H et al (2010) Highly predictive survival nomogram after upper urinary tract urothelial carcinoma. Cancer 116:3774–3784. doi:10.1002/cncr.25122 CrossRefPubMed Jeldres C, Sun M, Lughezzani G, Isbarn H, Shariat SF, Widmer H et al (2010) Highly predictive survival nomogram after upper urinary tract urothelial carcinoma. Cancer 116:3774–3784. doi:10.​1002/​cncr.​25122 CrossRefPubMed
8.
Zurück zum Zitat Lucca I, Kassouf W, Kapoor A, Fairey A, Rendon RA, Izawa JI et al (2015) The role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma following radical nephroureterectomy: a retrospective study. BJU Int 116:72–78. doi:10.1111/bju.12801 CrossRefPubMed Lucca I, Kassouf W, Kapoor A, Fairey A, Rendon RA, Izawa JI et al (2015) The role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma following radical nephroureterectomy: a retrospective study. BJU Int 116:72–78. doi:10.​1111/​bju.​12801 CrossRefPubMed
9.
Zurück zum Zitat Hellenthal NJ, Shariat SF, Margulis V, Karakiewicz PI, Roscigno M, Bolenz C et al (2009) Adjuvant chemotherapy for high risk upper tract urothelial carcinoma: results from the upper tract urothelial carcinoma collaboration. J Urol 182:900–906. doi:10.1016/j.juro.2009.05.011 CrossRefPubMed Hellenthal NJ, Shariat SF, Margulis V, Karakiewicz PI, Roscigno M, Bolenz C et al (2009) Adjuvant chemotherapy for high risk upper tract urothelial carcinoma: results from the upper tract urothelial carcinoma collaboration. J Urol 182:900–906. doi:10.​1016/​j.​juro.​2009.​05.​011 CrossRefPubMed
10.
Zurück zum Zitat Seisen T, Colin P, Hupertan V, Yates DR, Xylinas E, Nison L et al (2014) Postoperative nomogram to predict cancer-specific survival after radical nephroureterectomy in patients with localised and/or locally advanced upper tract urothelial carcinoma without metastasis. BJU Int 114:733–740. doi:10.1111/bju.12631 CrossRefPubMed Seisen T, Colin P, Hupertan V, Yates DR, Xylinas E, Nison L et al (2014) Postoperative nomogram to predict cancer-specific survival after radical nephroureterectomy in patients with localised and/or locally advanced upper tract urothelial carcinoma without metastasis. BJU Int 114:733–740. doi:10.​1111/​bju.​12631 CrossRefPubMed
11.
Zurück zum Zitat Fritsche H-M, Burger M, Svatek RS, Jeldres C, Karakiewicz PI, Novara G et al (2010) Characteristics and outcomes of patients with clinical T1 grade 3 urothelial carcinoma treated with radical cystectomy: results from an international cohort. Eur Urol 57:300–309. doi:10.1016/j.eururo.2009.09.024 CrossRefPubMed Fritsche H-M, Burger M, Svatek RS, Jeldres C, Karakiewicz PI, Novara G et al (2010) Characteristics and outcomes of patients with clinical T1 grade 3 urothelial carcinoma treated with radical cystectomy: results from an international cohort. Eur Urol 57:300–309. doi:10.​1016/​j.​eururo.​2009.​09.​024 CrossRefPubMed
13.
Zurück zum Zitat Sasaki Y, Sasaki T, Kawai T, Morikawa T, Matsusaka K, Kunita A et al (2014) HER2 protein overexpression and gene amplification in upper urinary tract urothelial carcinoma-an analysis of 171 patients. Int J Clin Exp Pathol 7:699–708PubMedPubMedCentral Sasaki Y, Sasaki T, Kawai T, Morikawa T, Matsusaka K, Kunita A et al (2014) HER2 protein overexpression and gene amplification in upper urinary tract urothelial carcinoma-an analysis of 171 patients. Int J Clin Exp Pathol 7:699–708PubMedPubMedCentral
14.
Zurück zum Zitat Ménard S, Fortis S, Castiglioni F, Agresti R, Balsari A (2001) HER2 as a prognostic factor in breast cancer. Oncology 61(Suppl 2):67–72CrossRefPubMed Ménard S, Fortis S, Castiglioni F, Agresti R, Balsari A (2001) HER2 as a prognostic factor in breast cancer. Oncology 61(Suppl 2):67–72CrossRefPubMed
17.
Zurück zum Zitat Bang Y-J, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet (London, England) 376:687–697. doi:10.1016/S0140-6736(10)61121-X CrossRef Bang Y-J, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet (London, England) 376:687–697. doi:10.​1016/​S0140-6736(10)61121-X CrossRef
19.
Zurück zum Zitat Bolenz C, Shariat SF, Karakiewicz PI, Ashfaq R, Ho R, Sagalowsky AI et al (2010) Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. BJU Int 106:1216–1222. doi:10.1111/j.1464-410X.2009.09190.x CrossRefPubMed Bolenz C, Shariat SF, Karakiewicz PI, Ashfaq R, Ho R, Sagalowsky AI et al (2010) Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. BJU Int 106:1216–1222. doi:10.​1111/​j.​1464-410X.​2009.​09190.​x CrossRefPubMed
23.
Zurück zum Zitat Vershasselt-Crinquette M, Colin P, Ouzzane A, Gnemmi V, Robin Y-M, Aubert S et al (2015) HER-2/AKT expression in upper urinary tract urothelial carcinoma: prognostic implications. J Urol 66:2439–2445. doi:10.1097/PAI.0b013e318241cab9 Vershasselt-Crinquette M, Colin P, Ouzzane A, Gnemmi V, Robin Y-M, Aubert S et al (2015) HER-2/AKT expression in upper urinary tract urothelial carcinoma: prognostic implications. J Urol 66:2439–2445. doi:10.​1097/​PAI.​0b013e318241cab9​
24.
Zurück zum Zitat Izquierdo L, Truan D, Mengual L, Mallofre C, Alcaraz A (2010) HER-2/AKT expression in upper urinary tract urothelial carcinoma: prognostic implications. Anticancer Res 30:2439–2445PubMed Izquierdo L, Truan D, Mengual L, Mallofre C, Alcaraz A (2010) HER-2/AKT expression in upper urinary tract urothelial carcinoma: prognostic implications. Anticancer Res 30:2439–2445PubMed
26.
Zurück zum Zitat Montironi R, Lopez-Beltran A (2005) The 2004 WHO classification of bladder tumors: a summary and commentary. Int J Surg Pathol 13:143–153CrossRefPubMed Montironi R, Lopez-Beltran A (2005) The 2004 WHO classification of bladder tumors: a summary and commentary. Int J Surg Pathol 13:143–153CrossRefPubMed
28.
30.
Zurück zum Zitat Xylinas E, Rink M, Robinson BD, Lotan Y, Babjuk M, Brisuda A et al (2013) Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy. Eur J Cancer 49:1889–1897. doi:10.1016/j.ejca.2013.02.001 CrossRefPubMed Xylinas E, Rink M, Robinson BD, Lotan Y, Babjuk M, Brisuda A et al (2013) Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy. Eur J Cancer 49:1889–1897. doi:10.​1016/​j.​ejca.​2013.​02.​001 CrossRefPubMed
31.
32.
Zurück zum Zitat Vershasselt-Crinquette M, Colin P, Ouzzane A, Gnemmi V, Robin Y-M, Aubert S et al (2012) Assessment of human epidermal growth factor receptor 2 status in urothelial carcinoma of the upper urinary tract: a study using dual-color in situ hybridization and immunohistochemistry. Appl Immunohistochem Mol Morphol 20:363–366. doi:10.1097/PAI.0b013e318241cab9 CrossRefPubMed Vershasselt-Crinquette M, Colin P, Ouzzane A, Gnemmi V, Robin Y-M, Aubert S et al (2012) Assessment of human epidermal growth factor receptor 2 status in urothelial carcinoma of the upper urinary tract: a study using dual-color in situ hybridization and immunohistochemistry. Appl Immunohistochem Mol Morphol 20:363–366. doi:10.​1097/​PAI.​0b013e318241cab9​ CrossRefPubMed
33.
Zurück zum Zitat Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM et al (2013) 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet (London, England) 382:1021–1028. doi:10.1016/S0140-6736(13)61094-6 CrossRef Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM et al (2013) 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet (London, England) 382:1021–1028. doi:10.​1016/​S0140-6736(13)61094-6 CrossRef
34.
Zurück zum Zitat Xylinas E, Kluth L, Mangal S, Roupret M, Karakiewicz PI, Shariat SF (2013) Predictive tools for clinical decision-making and counseling of patients with upper tract urothelial carcinoma. World J Urol 31:31–36. doi:10.1007/s00345-012-0947-5 CrossRefPubMed Xylinas E, Kluth L, Mangal S, Roupret M, Karakiewicz PI, Shariat SF (2013) Predictive tools for clinical decision-making and counseling of patients with upper tract urothelial carcinoma. World J Urol 31:31–36. doi:10.​1007/​s00345-012-0947-5 CrossRefPubMed
36.
Zurück zum Zitat Vassilakopoulou M, de la Motte Rouge T, Colin P, Ouzzane A, Khayat D, Dimopoulos M-A et al (2011) Outcomes after adjuvant chemotherapy in the treatment of high-risk urothelial carcinoma of the upper urinary tract (UUT-UC): results from a large multicenter collaborative study. Cancer 117:5500–5508. doi:10.1002/cncr.26172 CrossRefPubMed Vassilakopoulou M, de la Motte Rouge T, Colin P, Ouzzane A, Khayat D, Dimopoulos M-A et al (2011) Outcomes after adjuvant chemotherapy in the treatment of high-risk urothelial carcinoma of the upper urinary tract (UUT-UC): results from a large multicenter collaborative study. Cancer 117:5500–5508. doi:10.​1002/​cncr.​26172 CrossRefPubMed
39.
Zurück zum Zitat Oudard S, Culine S, Vano Y, Goldwasser F, Théodore C, Nguyen T et al (2015) Multicentre randomised phase II trial of gemcitabine + platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2. Eur J Cancer 51:45–54. doi:10.1016/j.ejca.2014.10.009 CrossRefPubMed Oudard S, Culine S, Vano Y, Goldwasser F, Théodore C, Nguyen T et al (2015) Multicentre randomised phase II trial of gemcitabine + platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2. Eur J Cancer 51:45–54. doi:10.​1016/​j.​ejca.​2014.​10.​009 CrossRefPubMed
40.
Zurück zum Zitat Wezel F, Erben P, Gaiser T, Budjan J, von Hardenberg J, Michel MS et al (2016) Complete and durable remission of human epidermal growth factor receptor 2-positive metastatic urothelial carcinoma following third-line treatment with trastuzumab and gemcitabine. Urol Int. doi:10.1159/000443280 PubMed Wezel F, Erben P, Gaiser T, Budjan J, von Hardenberg J, Michel MS et al (2016) Complete and durable remission of human epidermal growth factor receptor 2-positive metastatic urothelial carcinoma following third-line treatment with trastuzumab and gemcitabine. Urol Int. doi:10.​1159/​000443280 PubMed
Metadaten
Titel
HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC)
verfasst von
Francesco Soria
Marco Moschini
Andrea Haitel
Gregory J. Wirth
Jose A. Karam
Christopher G. Wood
Morgan Rouprêt
Vitaly Margulis
Pierre I. Karakiewicz
Alberto Briganti
Jay D. Raman
Solene-Florence Kammerer-Jacquet
Romain Mathieu
Karim Bensalah
Yair Lotan
Mehmet Özsoy
Mesut Remzi
Kilian M. Gust
Shahrokh F. Shariat
Publikationsdatum
07.06.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
World Journal of Urology / Ausgabe 2/2017
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-016-1871-x

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