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, Vol. 10, No. 3, 03.2021, p. 1048-1055.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -