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Homogeneous MMR Deficiency Throughout the Entire Tumor Mass Occurs in a Subset of Colorectal Neuroendocrine Carcinomas

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Homogeneous MMR Deficiency Throughout the Entire Tumor Mass Occurs in a Subset of Colorectal Neuroendocrine Carcinomas. / Fraune, Christoph; Simon, Ronald; Hube-Magg, Claudia; Makrypidi-Fraune, Georgia; Kluth, Martina; Büscheck, Franziska; Amin, Tania; Viol, Fabrice; Fehrle, Wilfrid; Dum, David; Höflmayer, Doris; Burandt, Eike; Clauditz, Till Sebastian; Perez, Daniel; Izbicki, Jakob; Wilczak, Waldemar; Sauter, Guido; Steurer, Stefan; Schrader, Jörg.

In: ENDOCR PATHOL, Vol. 31, No. 2, 06.2020, p. 182-189.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Fraune, C, Simon, R, Hube-Magg, C, Makrypidi-Fraune, G, Kluth, M, Büscheck, F, Amin, T, Viol, F, Fehrle, W, Dum, D, Höflmayer, D, Burandt, E, Clauditz, TS, Perez, D, Izbicki, J, Wilczak, W, Sauter, G, Steurer, S & Schrader, J 2020, 'Homogeneous MMR Deficiency Throughout the Entire Tumor Mass Occurs in a Subset of Colorectal Neuroendocrine Carcinomas', ENDOCR PATHOL, vol. 31, no. 2, pp. 182-189. https://doi.org/10.1007/s12022-020-09612-7

APA

Fraune, C., Simon, R., Hube-Magg, C., Makrypidi-Fraune, G., Kluth, M., Büscheck, F., Amin, T., Viol, F., Fehrle, W., Dum, D., Höflmayer, D., Burandt, E., Clauditz, T. S., Perez, D., Izbicki, J., Wilczak, W., Sauter, G., Steurer, S., & Schrader, J. (2020). Homogeneous MMR Deficiency Throughout the Entire Tumor Mass Occurs in a Subset of Colorectal Neuroendocrine Carcinomas. ENDOCR PATHOL, 31(2), 182-189. https://doi.org/10.1007/s12022-020-09612-7

Vancouver

Fraune C, Simon R, Hube-Magg C, Makrypidi-Fraune G, Kluth M, Büscheck F et al. Homogeneous MMR Deficiency Throughout the Entire Tumor Mass Occurs in a Subset of Colorectal Neuroendocrine Carcinomas. ENDOCR PATHOL. 2020 Jun;31(2):182-189. https://doi.org/10.1007/s12022-020-09612-7

Bibtex

@article{0789fe294f1b47f8b10b507b4ebcca23,
title = "Homogeneous MMR Deficiency Throughout the Entire Tumor Mass Occurs in a Subset of Colorectal Neuroendocrine Carcinomas",
abstract = "Neuroendocrine neoplasms comprise a heterogeneous group of tumors, categorized into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) depending on tumor differentiation. NECs and high-grade NETs (G3) confer a poor prognosis, demanding novel treatment strategies such as immune checkpoint inhibition in tumors with microsatellite instability (MSI). To study any possible intratumoral heterogeneity of MSI, a tissue microarray (TMA) containing 199 NETs and 40 NECs was constructed to screen for MSI using immunohistochemistry (IHC) for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. Four cases suspicious for MSI were identified. Validation of MSI by repeated IHC on large sections and polymerase chain reaction (PCR)-based analysis using the {"}Bethesda Panel{"} confirmed MSI in 3 cecal NECs. One pancreatic NET G3 with MSI-compatible TMA results was MMR intact on large section IHC and microsatellite stable (MSS). The remaining 235 tumors exhibited intact MMR. Protein loss of MLH1/PMS2 was found in two and MSH6 loss in one cancer with MSI. Large section IHC on all available tumor-containing tissue blocks in NECs with MSI did not identify aberrant tumor areas with intact MMR. Our data indicate that MSI is common in colorectal NECs (3 out of 10) but highly infrequent in neuroendocrine neoplasms from many other sites. The lack of intratumoral heterogeneity of MMR deficiency suggests early development of MSI during tumorigenesis in a subset of colorectal NECs and indicates that microsatellite status obtained from small biopsies may be representative for the entire cancer mass.",
author = "Christoph Fraune and Ronald Simon and Claudia Hube-Magg and Georgia Makrypidi-Fraune and Martina Kluth and Franziska B{\"u}scheck and Tania Amin and Fabrice Viol and Wilfrid Fehrle and David Dum and Doris H{\"o}flmayer and Eike Burandt and Clauditz, {Till Sebastian} and Daniel Perez and Jakob Izbicki and Waldemar Wilczak and Guido Sauter and Stefan Steurer and J{\"o}rg Schrader",
year = "2020",
month = jun,
doi = "10.1007/s12022-020-09612-7",
language = "English",
volume = "31",
pages = "182--189",
journal = "ENDOCR PATHOL",
issn = "1046-3976",
publisher = "Humana Press",
number = "2",

}

RIS

TY - JOUR

T1 - Homogeneous MMR Deficiency Throughout the Entire Tumor Mass Occurs in a Subset of Colorectal Neuroendocrine Carcinomas

AU - Fraune, Christoph

AU - Simon, Ronald

AU - Hube-Magg, Claudia

AU - Makrypidi-Fraune, Georgia

AU - Kluth, Martina

AU - Büscheck, Franziska

AU - Amin, Tania

AU - Viol, Fabrice

AU - Fehrle, Wilfrid

AU - Dum, David

AU - Höflmayer, Doris

AU - Burandt, Eike

AU - Clauditz, Till Sebastian

AU - Perez, Daniel

AU - Izbicki, Jakob

AU - Wilczak, Waldemar

AU - Sauter, Guido

AU - Steurer, Stefan

AU - Schrader, Jörg

PY - 2020/6

Y1 - 2020/6

N2 - Neuroendocrine neoplasms comprise a heterogeneous group of tumors, categorized into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) depending on tumor differentiation. NECs and high-grade NETs (G3) confer a poor prognosis, demanding novel treatment strategies such as immune checkpoint inhibition in tumors with microsatellite instability (MSI). To study any possible intratumoral heterogeneity of MSI, a tissue microarray (TMA) containing 199 NETs and 40 NECs was constructed to screen for MSI using immunohistochemistry (IHC) for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. Four cases suspicious for MSI were identified. Validation of MSI by repeated IHC on large sections and polymerase chain reaction (PCR)-based analysis using the "Bethesda Panel" confirmed MSI in 3 cecal NECs. One pancreatic NET G3 with MSI-compatible TMA results was MMR intact on large section IHC and microsatellite stable (MSS). The remaining 235 tumors exhibited intact MMR. Protein loss of MLH1/PMS2 was found in two and MSH6 loss in one cancer with MSI. Large section IHC on all available tumor-containing tissue blocks in NECs with MSI did not identify aberrant tumor areas with intact MMR. Our data indicate that MSI is common in colorectal NECs (3 out of 10) but highly infrequent in neuroendocrine neoplasms from many other sites. The lack of intratumoral heterogeneity of MMR deficiency suggests early development of MSI during tumorigenesis in a subset of colorectal NECs and indicates that microsatellite status obtained from small biopsies may be representative for the entire cancer mass.

AB - Neuroendocrine neoplasms comprise a heterogeneous group of tumors, categorized into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) depending on tumor differentiation. NECs and high-grade NETs (G3) confer a poor prognosis, demanding novel treatment strategies such as immune checkpoint inhibition in tumors with microsatellite instability (MSI). To study any possible intratumoral heterogeneity of MSI, a tissue microarray (TMA) containing 199 NETs and 40 NECs was constructed to screen for MSI using immunohistochemistry (IHC) for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. Four cases suspicious for MSI were identified. Validation of MSI by repeated IHC on large sections and polymerase chain reaction (PCR)-based analysis using the "Bethesda Panel" confirmed MSI in 3 cecal NECs. One pancreatic NET G3 with MSI-compatible TMA results was MMR intact on large section IHC and microsatellite stable (MSS). The remaining 235 tumors exhibited intact MMR. Protein loss of MLH1/PMS2 was found in two and MSH6 loss in one cancer with MSI. Large section IHC on all available tumor-containing tissue blocks in NECs with MSI did not identify aberrant tumor areas with intact MMR. Our data indicate that MSI is common in colorectal NECs (3 out of 10) but highly infrequent in neuroendocrine neoplasms from many other sites. The lack of intratumoral heterogeneity of MMR deficiency suggests early development of MSI during tumorigenesis in a subset of colorectal NECs and indicates that microsatellite status obtained from small biopsies may be representative for the entire cancer mass.

U2 - 10.1007/s12022-020-09612-7

DO - 10.1007/s12022-020-09612-7

M3 - SCORING: Journal article

C2 - 32144630

VL - 31

SP - 182

EP - 189

JO - ENDOCR PATHOL

JF - ENDOCR PATHOL

SN - 1046-3976

IS - 2

ER -