KRT20, KRT5, ESR1 and ERBB2 Expression Can Predict Pathologic Outcome in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer

Jütte, Hendrik; Reike, Moritz; Wirtz, Ralph M.; Kriegmair, Maximilian; Erben, Philipp; Tully, Karl; Weyerer, Veronika; Eckstein, Markus; Hartmann, Arndt; Eidt, Sebastian; Wezel, Felix; Bolenz, Christian; Tannapfel, Andrea; Noldus, Joachim; Roghmann, Florian

doi:10.3390/jpm11060473

Open AccessArticle

KRT20, KRT5, ESR1 and ERBB2 Expression Can Predict Pathologic Outcome in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer

by

Hendrik Jütte

^1,*,†,‡,

Moritz Reike

^2,†,‡,

Ralph M. Wirtz

^3,‡,

Maximilian Kriegmair

^4,‡,

Philipp Erben

^4,‡,

Karl Tully

^2,‡,

Veronika Weyerer

^5,‡,

Markus Eckstein

^5,‡,

Arndt Hartmann

^5,‡,

Sebastian Eidt

⁶

,

Felix Wezel

^7,‡

,

Christian Bolenz

^7,‡,

Andrea Tannapfel

¹,

Joachim Noldus

^2,‡ and

Florian Roghmann

^2,‡

¹

Institute of Pathology, Ruhr-University Bochum, 44789 Bochum, Germany

²

Department of Urology, Marien Hospital, Ruhr-University Bochum, 44625 Herne, Germany

³

Stratifyer Molecular Pathology GmbH, 50935 Cologne, Germany

⁴

Department of Urology and Urosurgery, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany

⁵

Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany

⁶

Institute of Pathology, St. Elisabeth Hospital, 50935 Cologne, Germany

⁷

Department of Urology, University Hospital Ulm, University of Ulm, 89081 Ulm, Germany

^*

Author to whom correspondence should be addressed.

^†

Denotes equal contribution.

^‡

On behalf of the BRIDGE Consortium e.V.

J. Pers. Med. 2021, 11(6), 473; https://doi.org/10.3390/jpm11060473

Submission received: 30 March 2021 / Revised: 17 May 2021 / Accepted: 18 May 2021 / Published: 26 May 2021

(This article belongs to the Special Issue Bladder Cancer and Personalized Treatment)

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Abstract

Patients with muscle-invasive bladder cancer (MIBC) that underwent neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) show improved overall survival, especially those with pathological complete response (pCR). The response to NAC according to molecular subtypes has been discussed. Molecular targets such as estrogen receptor (ESR1) and human epidermal growth factor receptor 2 (ERBB2) play an important role in breast cancer management and have also been associated with urothelial bladder cancer. Hence, the association of Keratin 20 (KRT20) Keratin 5 (KRT5), ESR1, and ERBB2 mRNA expression in MIBC at transurethral resection (TUR-BT) with pCR after NAC was analyzed retrospectively. Formalin-fixed paraffin-embedded tumour tissue samples from TUR-BT of 54 patients (42 males, 12 females, median age of 64) with MIBC were analyzed for KRT20, KRT5, ESR1, and ERBB2 mRNA expression. After NAC, RC was performed, and the specimens were evaluated for pCR. Statistical analyses comprised nonparametric and chi² testing, partition models, and Spearman correlation analyses. After NAC, 22 out of 54 patients (40.7%) had pCR. Tumours with an elevated expression of markers associated with luminal differentiation (KRT20, ERBB2, ESR1) were associated with a higher chance of pCR (55% vs. 15.8%, p = 0.009). Elevated ERBB2 expression was positively correlated with luminal expression features such as KRT20, and negatively with basal characteristics such as KRT5. Patients with MIBC showing a high expression of ERBB2, ESR1, or KRT20 have a significantly higher chance of pCR following NAC. These findings might improve patient selection for NAC in MIBC.

Keywords: bladder cancer; chemotherapy; muscle invasive; risk stratification; subtype

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MDPI and ACS Style

Jütte, H.; Reike, M.; Wirtz, R.M.; Kriegmair, M.; Erben, P.; Tully, K.; Weyerer, V.; Eckstein, M.; Hartmann, A.; Eidt, S.; et al. KRT20, KRT5, ESR1 and ERBB2 Expression Can Predict Pathologic Outcome in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer. J. Pers. Med. 2021, 11, 473. https://doi.org/10.3390/jpm11060473

AMA Style

Jütte H, Reike M, Wirtz RM, Kriegmair M, Erben P, Tully K, Weyerer V, Eckstein M, Hartmann A, Eidt S, et al. KRT20, KRT5, ESR1 and ERBB2 Expression Can Predict Pathologic Outcome in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer. Journal of Personalized Medicine. 2021; 11(6):473. https://doi.org/10.3390/jpm11060473

Chicago/Turabian Style

Jütte, Hendrik, Moritz Reike, Ralph M. Wirtz, Maximilian Kriegmair, Philipp Erben, Karl Tully, Veronika Weyerer, Markus Eckstein, Arndt Hartmann, Sebastian Eidt, and et al. 2021. "KRT20, KRT5, ESR1 and ERBB2 Expression Can Predict Pathologic Outcome in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer" Journal of Personalized Medicine 11, no. 6: 473. https://doi.org/10.3390/jpm11060473

APA Style

Jütte, H., Reike, M., Wirtz, R. M., Kriegmair, M., Erben, P., Tully, K., Weyerer, V., Eckstein, M., Hartmann, A., Eidt, S., Wezel, F., Bolenz, C., Tannapfel, A., Noldus, J., & Roghmann, F. (2021). KRT20, KRT5, ESR1 and ERBB2 Expression Can Predict Pathologic Outcome in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer. Journal of Personalized Medicine, 11(6), 473. https://doi.org/10.3390/jpm11060473

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KRT20, KRT5, ESR1 and ERBB2 Expression Can Predict Pathologic Outcome in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer

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