Mismatch repair deficiency occurs very rarely in seminomas

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Mismatch repair deficiency occurs very rarely in seminomas. / Dum, David; Steurer, Stefan; Simon, Ronald; Zimmermann, Pia Victoria; Burandt, Eike; Clauditz, Till Sebastian; Fisch, Margit; Rink, Michael; Dahlem, Roland; Höppner, Wolfgang; Zecha, Henrik; Doh, Ousman; Matthies, Cord; Wilczak, Waldemar; Sauter, Guido; Fraune, Christoph.

in: TRANSL ANDROL UROL, Jahrgang 10, Nr. 3, 03.2021, S. 1048-1055.

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@article{1796ebee79e14655b57934f4f8ea74ff,
title = "Mismatch repair deficiency occurs very rarely in seminomas",
abstract = "Background: Dense tumor-associated lymphocyte infiltration is linked to mismatch repair (MMR) deficiency in colorectal and endometrial cancer. MMR deficiency is of high clinical importance as MMR deficient cancers tend to react favorably to treatment with immune checkpoint inhibitors. Strong lymphocytic infiltration is a morphological hallmark of seminomas. We thus asked whether seminomas may exhibit MMR deficiency at relevant frequency.Methods: To screen for tumors with MMR deficiency, protein expression of MLH1, PMS2, MSH2, and MSH6 was analyzed by immunohistochemistry (IHC) on a tissue microarray (TMA) containing 574 seminomas.Results: In total, 536 cases were evaluable resulting in 481 seminomas with unequivocally intact MMR protein expression. In 55 cancers, one or several IHC stains were equivocal and lacked detectable MMR protein in both tumor and stromal cells. Large section IHC analysis of all 55 equivocal cases demonstrated substantial staining issues due to improper fixation in 54 cases and identified one tumor with clear-cut MLH1 and PMS2 protein loss. This seminoma showed homogeneous loss of MLH1 and PMS2 in the entire tumor mass whereas minor adjacent foci of associated germ cell neoplasia in situ (GCNIS) were MMR intact. Polymerase chain reaction (PCR) analysis using the 5 microsatellite loci of the {"}Bethesda Panel{"} revealed instability in 1 of 4 interpretable loci ({"}MSI-low{"}) and additional instability of the complex tetra-penta repeat locus MYCL1 in this tumor.Conclusions: In summary, one single seminoma with MMR deficiency, characterized by protein loss of MLH1 and PMS2, was identified among 536 interpretable seminomas (0.19%). MMR deficiency is not a relevant determinant of lymphocyte influx in seminoma.",
author = "David Dum and Stefan Steurer and Ronald Simon and Zimmermann, {Pia Victoria} and Eike Burandt and Clauditz, {Till Sebastian} and Margit Fisch and Michael Rink and Roland Dahlem and Wolfgang H{\"o}ppner and Henrik Zecha and Ousman Doh and Cord Matthies and Waldemar Wilczak and Guido Sauter and Christoph Fraune",
note = "2021 Translational Andrology and Urology. All rights reserved.",
year = "2021",
month = mar,
doi = "10.21037/tau-20-1355",
language = "English",
volume = "10",
pages = "1048--1055",
journal = "TRANSL ANDROL UROL",
issn = "2223-4683",
publisher = "AME Publishing Company",
number = "3",

}

RIS

TY - JOUR

T1 - Mismatch repair deficiency occurs very rarely in seminomas

AU - Dum, David

AU - Steurer, Stefan

AU - Simon, Ronald

AU - Zimmermann, Pia Victoria

AU - Burandt, Eike

AU - Clauditz, Till Sebastian

AU - Fisch, Margit

AU - Rink, Michael

AU - Dahlem, Roland

AU - Höppner, Wolfgang

AU - Zecha, Henrik

AU - Doh, Ousman

AU - Matthies, Cord

AU - Wilczak, Waldemar

AU - Sauter, Guido

AU - Fraune, Christoph

N1 - 2021 Translational Andrology and Urology. All rights reserved.

PY - 2021/3

Y1 - 2021/3

N2 - Background: Dense tumor-associated lymphocyte infiltration is linked to mismatch repair (MMR) deficiency in colorectal and endometrial cancer. MMR deficiency is of high clinical importance as MMR deficient cancers tend to react favorably to treatment with immune checkpoint inhibitors. Strong lymphocytic infiltration is a morphological hallmark of seminomas. We thus asked whether seminomas may exhibit MMR deficiency at relevant frequency.Methods: To screen for tumors with MMR deficiency, protein expression of MLH1, PMS2, MSH2, and MSH6 was analyzed by immunohistochemistry (IHC) on a tissue microarray (TMA) containing 574 seminomas.Results: In total, 536 cases were evaluable resulting in 481 seminomas with unequivocally intact MMR protein expression. In 55 cancers, one or several IHC stains were equivocal and lacked detectable MMR protein in both tumor and stromal cells. Large section IHC analysis of all 55 equivocal cases demonstrated substantial staining issues due to improper fixation in 54 cases and identified one tumor with clear-cut MLH1 and PMS2 protein loss. This seminoma showed homogeneous loss of MLH1 and PMS2 in the entire tumor mass whereas minor adjacent foci of associated germ cell neoplasia in situ (GCNIS) were MMR intact. Polymerase chain reaction (PCR) analysis using the 5 microsatellite loci of the "Bethesda Panel" revealed instability in 1 of 4 interpretable loci ("MSI-low") and additional instability of the complex tetra-penta repeat locus MYCL1 in this tumor.Conclusions: In summary, one single seminoma with MMR deficiency, characterized by protein loss of MLH1 and PMS2, was identified among 536 interpretable seminomas (0.19%). MMR deficiency is not a relevant determinant of lymphocyte influx in seminoma.

AB - Background: Dense tumor-associated lymphocyte infiltration is linked to mismatch repair (MMR) deficiency in colorectal and endometrial cancer. MMR deficiency is of high clinical importance as MMR deficient cancers tend to react favorably to treatment with immune checkpoint inhibitors. Strong lymphocytic infiltration is a morphological hallmark of seminomas. We thus asked whether seminomas may exhibit MMR deficiency at relevant frequency.Methods: To screen for tumors with MMR deficiency, protein expression of MLH1, PMS2, MSH2, and MSH6 was analyzed by immunohistochemistry (IHC) on a tissue microarray (TMA) containing 574 seminomas.Results: In total, 536 cases were evaluable resulting in 481 seminomas with unequivocally intact MMR protein expression. In 55 cancers, one or several IHC stains were equivocal and lacked detectable MMR protein in both tumor and stromal cells. Large section IHC analysis of all 55 equivocal cases demonstrated substantial staining issues due to improper fixation in 54 cases and identified one tumor with clear-cut MLH1 and PMS2 protein loss. This seminoma showed homogeneous loss of MLH1 and PMS2 in the entire tumor mass whereas minor adjacent foci of associated germ cell neoplasia in situ (GCNIS) were MMR intact. Polymerase chain reaction (PCR) analysis using the 5 microsatellite loci of the "Bethesda Panel" revealed instability in 1 of 4 interpretable loci ("MSI-low") and additional instability of the complex tetra-penta repeat locus MYCL1 in this tumor.Conclusions: In summary, one single seminoma with MMR deficiency, characterized by protein loss of MLH1 and PMS2, was identified among 536 interpretable seminomas (0.19%). MMR deficiency is not a relevant determinant of lymphocyte influx in seminoma.

U2 - 10.21037/tau-20-1355

DO - 10.21037/tau-20-1355

M3 - SCORING: Journal article

C2 - 33850739

VL - 10

SP - 1048

EP - 1055

JO - TRANSL ANDROL UROL

JF - TRANSL ANDROL UROL

SN - 2223-4683

IS - 3

ER -