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MMR deficiency in urothelial carcinoma of the bladder presents with temporal and spatial homogeneity throughout the tumor mass

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MMR deficiency in urothelial carcinoma of the bladder presents with temporal and spatial homogeneity throughout the tumor mass. / Fraune, Christoph; Simon, Ronald; Hube-Magg, Claudia; Makrypidi-Fraune, Georgia; Kähler, Christian; Kluth, Martina; Höflmayer, Doris; Büscheck, Franziska; Dum, David; Luebke, Andreas M; Burandt, Eike; Clauditz, Till Sebastian; Wilczak, Waldemar; Sauter, Guido; Steurer, Stefan.

in: UROL ONCOL-SEMIN ORI, Jahrgang 38, Nr. 5, 05.2020, S. 488-495.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Fraune, C, Simon, R, Hube-Magg, C, Makrypidi-Fraune, G, Kähler, C, Kluth, M, Höflmayer, D, Büscheck, F, Dum, D, Luebke, AM, Burandt, E, Clauditz, TS, Wilczak, W, Sauter, G & Steurer, S 2020, 'MMR deficiency in urothelial carcinoma of the bladder presents with temporal and spatial homogeneity throughout the tumor mass', UROL ONCOL-SEMIN ORI, Jg. 38, Nr. 5, S. 488-495. https://doi.org/10.1016/j.urolonc.2019.12.012

APA

Fraune, C., Simon, R., Hube-Magg, C., Makrypidi-Fraune, G., Kähler, C., Kluth, M., Höflmayer, D., Büscheck, F., Dum, D., Luebke, A. M., Burandt, E., Clauditz, T. S., Wilczak, W., Sauter, G., & Steurer, S. (2020). MMR deficiency in urothelial carcinoma of the bladder presents with temporal and spatial homogeneity throughout the tumor mass. UROL ONCOL-SEMIN ORI, 38(5), 488-495. https://doi.org/10.1016/j.urolonc.2019.12.012

Vancouver

Fraune C, Simon R, Hube-Magg C, Makrypidi-Fraune G, Kähler C, Kluth M et al. MMR deficiency in urothelial carcinoma of the bladder presents with temporal and spatial homogeneity throughout the tumor mass. UROL ONCOL-SEMIN ORI. 2020 Mai;38(5):488-495. https://doi.org/10.1016/j.urolonc.2019.12.012

Bibtex

@article{9ff6487d49ee44c2bbd7f3d4e5ad43db,
title = "MMR deficiency in urothelial carcinoma of the bladder presents with temporal and spatial homogeneity throughout the tumor mass",
abstract = "BACKGROUND: Microsatellite instability (MSI), a hypermutator phenotype described in many cancers, has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents a potential obstacle for the analysis of predicitive biomarkers. MSI has been reported in bladder cancer, but data on the possible extent of intratumoral heterogeneity are lacking.METHODS: To study MSI heterogeneity in bladder cancer, a tissue microarray (TMA) comprising 598 muscle-invasive urothelial carcinomas of the bladder was utilized to screen for MSI by immunhistochemistry with antibodies for MLH1, PMS2, MSH2, and MSH6.RESULTS: In 9 cases suspicious for MSI, MMR status was further evaluated by large section examination and polymerase chain reaction (PCR)-based analysis of microsatellites ({"}Bethesda panel{"}) resulting in the identification of 5 validated MSI cases from 448 interpretable cancers (prevalence 1.1%). MMR deficiency always involved PMS2 loss, in 3 cases with additional loss or reduction of MLH1 expression. Four cancers were MSI-high and 1 was MSI-low in the PCR analysis. Parallel sequencing revealed an inactivating MLH1 mutation in 1 tumor but no further known pathogenic MMR gene mutations were found. Immunostaining of all available 72 cancer-containing tissue blocks of the 5 confirmed bladder cancer with MSI including prior and subsequent biopsies showed complete homogeneity of the MMR protein defects and the status of the 4 MMR proteins did not markedly change in sequential resections. In all 4 cases with noninvasive precursor lesions, MSI was also detectable.CONCLUSION: These data suggest that MSI occurs early in invasive bladder cancer and immunohistochemical MMR analysis on limited biopsy material is sufficient to estimate MMR status of the entire cancer mass.",
author = "Christoph Fraune and Ronald Simon and Claudia Hube-Magg and Georgia Makrypidi-Fraune and Christian K{\"a}hler and Martina Kluth and Doris H{\"o}flmayer and Franziska B{\"u}scheck and David Dum and Luebke, {Andreas M} and Eike Burandt and Clauditz, {Till Sebastian} and Waldemar Wilczak and Guido Sauter and Stefan Steurer",
note = "Copyright {\textcopyright} 2019 Elsevier Inc. All rights reserved.",
year = "2020",
month = may,
doi = "10.1016/j.urolonc.2019.12.012",
language = "English",
volume = "38",
pages = "488--495",
journal = "UROL ONCOL-SEMIN ORI",
issn = "1078-1439",
publisher = "Elsevier Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - MMR deficiency in urothelial carcinoma of the bladder presents with temporal and spatial homogeneity throughout the tumor mass

AU - Fraune, Christoph

AU - Simon, Ronald

AU - Hube-Magg, Claudia

AU - Makrypidi-Fraune, Georgia

AU - Kähler, Christian

AU - Kluth, Martina

AU - Höflmayer, Doris

AU - Büscheck, Franziska

AU - Dum, David

AU - Luebke, Andreas M

AU - Burandt, Eike

AU - Clauditz, Till Sebastian

AU - Wilczak, Waldemar

AU - Sauter, Guido

AU - Steurer, Stefan

N1 - Copyright © 2019 Elsevier Inc. All rights reserved.

PY - 2020/5

Y1 - 2020/5

N2 - BACKGROUND: Microsatellite instability (MSI), a hypermutator phenotype described in many cancers, has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents a potential obstacle for the analysis of predicitive biomarkers. MSI has been reported in bladder cancer, but data on the possible extent of intratumoral heterogeneity are lacking.METHODS: To study MSI heterogeneity in bladder cancer, a tissue microarray (TMA) comprising 598 muscle-invasive urothelial carcinomas of the bladder was utilized to screen for MSI by immunhistochemistry with antibodies for MLH1, PMS2, MSH2, and MSH6.RESULTS: In 9 cases suspicious for MSI, MMR status was further evaluated by large section examination and polymerase chain reaction (PCR)-based analysis of microsatellites ("Bethesda panel") resulting in the identification of 5 validated MSI cases from 448 interpretable cancers (prevalence 1.1%). MMR deficiency always involved PMS2 loss, in 3 cases with additional loss or reduction of MLH1 expression. Four cancers were MSI-high and 1 was MSI-low in the PCR analysis. Parallel sequencing revealed an inactivating MLH1 mutation in 1 tumor but no further known pathogenic MMR gene mutations were found. Immunostaining of all available 72 cancer-containing tissue blocks of the 5 confirmed bladder cancer with MSI including prior and subsequent biopsies showed complete homogeneity of the MMR protein defects and the status of the 4 MMR proteins did not markedly change in sequential resections. In all 4 cases with noninvasive precursor lesions, MSI was also detectable.CONCLUSION: These data suggest that MSI occurs early in invasive bladder cancer and immunohistochemical MMR analysis on limited biopsy material is sufficient to estimate MMR status of the entire cancer mass.

AB - BACKGROUND: Microsatellite instability (MSI), a hypermutator phenotype described in many cancers, has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents a potential obstacle for the analysis of predicitive biomarkers. MSI has been reported in bladder cancer, but data on the possible extent of intratumoral heterogeneity are lacking.METHODS: To study MSI heterogeneity in bladder cancer, a tissue microarray (TMA) comprising 598 muscle-invasive urothelial carcinomas of the bladder was utilized to screen for MSI by immunhistochemistry with antibodies for MLH1, PMS2, MSH2, and MSH6.RESULTS: In 9 cases suspicious for MSI, MMR status was further evaluated by large section examination and polymerase chain reaction (PCR)-based analysis of microsatellites ("Bethesda panel") resulting in the identification of 5 validated MSI cases from 448 interpretable cancers (prevalence 1.1%). MMR deficiency always involved PMS2 loss, in 3 cases with additional loss or reduction of MLH1 expression. Four cancers were MSI-high and 1 was MSI-low in the PCR analysis. Parallel sequencing revealed an inactivating MLH1 mutation in 1 tumor but no further known pathogenic MMR gene mutations were found. Immunostaining of all available 72 cancer-containing tissue blocks of the 5 confirmed bladder cancer with MSI including prior and subsequent biopsies showed complete homogeneity of the MMR protein defects and the status of the 4 MMR proteins did not markedly change in sequential resections. In all 4 cases with noninvasive precursor lesions, MSI was also detectable.CONCLUSION: These data suggest that MSI occurs early in invasive bladder cancer and immunohistochemical MMR analysis on limited biopsy material is sufficient to estimate MMR status of the entire cancer mass.

U2 - 10.1016/j.urolonc.2019.12.012

DO - 10.1016/j.urolonc.2019.12.012

M3 - SCORING: Journal article

C2 - 32067846

VL - 38

SP - 488

EP - 495

JO - UROL ONCOL-SEMIN ORI

JF - UROL ONCOL-SEMIN ORI

SN - 1078-1439

IS - 5

ER -