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Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability, and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer

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Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability, and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer. / Wilczak, Waldemar; Rashed, Semin; Hube-Magg, Claudia; Kluth, Martina; Simon, Ronald; Büscheck, Franziska; Clauditz, Till Sebastian; Grupp, Katharina; Minner, Sarah; Tsourlakis, Maria Christina; Koop, Christina; Graefen, Markus; Adam, Meike; Haese, Alexander; Wittmer, Corinna; Sauter, Guido; Izbicki, Jakob Robert; Huland, Hartwig; Schlomm, Thorsten; Steurer, Stefan; Krech, Till; Lebok, Patrick.

In: CARCINOGENESIS, Vol. 38, No. 1, 01.2017, p. 19-27.

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

Harvard

Wilczak, W, Rashed, S, Hube-Magg, C, Kluth, M, Simon, R, Büscheck, F, Clauditz, TS, Grupp, K, Minner, S, Tsourlakis, MC, Koop, C, Graefen, M, Adam, M, Haese, A, Wittmer, C, Sauter, G, Izbicki, JR, Huland, H, Schlomm, T, Steurer, S, Krech, T & Lebok, P 2017, 'Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability, and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer', CARCINOGENESIS, vol. 38, no. 1, pp. 19-27. https://doi.org/10.1093/carcin/bgw116

APA

Wilczak, W., Rashed, S., Hube-Magg, C., Kluth, M., Simon, R., Büscheck, F., Clauditz, T. S., Grupp, K., Minner, S., Tsourlakis, M. C., Koop, C., Graefen, M., Adam, M., Haese, A., Wittmer, C., Sauter, G., Izbicki, J. R., Huland, H., Schlomm, T., ... Lebok, P. (2017). Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability, and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer. CARCINOGENESIS, 38(1), 19-27. https://doi.org/10.1093/carcin/bgw116

Vancouver

Wilczak W, Rashed S, Hube-Magg C, Kluth M, Simon R, Büscheck F et al. Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability, and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer. CARCINOGENESIS. 2017 Jan;38(1):19-27. https://doi.org/10.1093/carcin/bgw116

Bibtex

@article{1c5576efb7c14a799d019cc352854875,
title = "Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability, and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer",
abstract = "DNA mismatch repair (MMR) is integral to the maintenance of genetic stability. We aimed to evaluate the clinical impact of MMR gene expression in prostate cancer. The MMR genes MSH6, MLH1 and PMS2 were analyzed by immunohistochemistry on a tissue microarray containing 11 152 prostate cancer specimens. Results were compared with ERG status and deletions of PTEN, 3p13, 5q21, and 6q15. MSH6, MLH1 and PMS2 expression was detectable in 89.5%, 85.4% and 85.0% of cancers, and was particularly strong in cancers with advanced pathological tumor stage (p<0.0001 each), high Gleason grade (p<0.0001 each), nodal metastasis (p≤0.0083), and early biochemical recurrence (p<0.0001). High levels of MMR gene expression paralleled features of genetic instability, such as the number of genomic deletions per cancer; strong expression of all three MMR genes was found in 24%, 29%, 30%, 33% and 42% of cancers with no, one, two, three or four to five deletions (p<0.0001). The prognostic value of the analyzed MMR genes was largely driven by the subset of cancers lacking ERG-fusion (p<0.0001), while the prognostic impact of MMR gene overexpression was only marginal in ERG-positive cancers. Multivariate analyses suggested an independent prognostic relevance of MMR genes in ERG-negative prostate cancers when compared to prognostic parameters available at the time of initial biopsy. In conclusion, MMR overexpression is common in prostate cancer, and is linked to poor outcome as well as features indicating genetic instability. ERG-fusion should be analyzed along with MMR gene expression in potential clinical tests.",
author = "Waldemar Wilczak and Semin Rashed and Claudia Hube-Magg and Martina Kluth and Ronald Simon and Franziska B{\"u}scheck and Clauditz, {Till Sebastian} and Katharina Grupp and Sarah Minner and Tsourlakis, {Maria Christina} and Christina Koop and Markus Graefen and Meike Adam and Alexander Haese and Corinna Wittmer and Guido Sauter and Izbicki, {Jakob Robert} and Hartwig Huland and Thorsten Schlomm and Stefan Steurer and Till Krech and Patrick Lebok",
note = "{\textcopyright} The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.",
year = "2017",
month = jan,
doi = "10.1093/carcin/bgw116",
language = "English",
volume = "38",
pages = "19--27",
journal = "CARCINOGENESIS",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "1",

}

RIS

TY - JOUR

T1 - Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability, and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer

AU - Wilczak, Waldemar

AU - Rashed, Semin

AU - Hube-Magg, Claudia

AU - Kluth, Martina

AU - Simon, Ronald

AU - Büscheck, Franziska

AU - Clauditz, Till Sebastian

AU - Grupp, Katharina

AU - Minner, Sarah

AU - Tsourlakis, Maria Christina

AU - Koop, Christina

AU - Graefen, Markus

AU - Adam, Meike

AU - Haese, Alexander

AU - Wittmer, Corinna

AU - Sauter, Guido

AU - Izbicki, Jakob Robert

AU - Huland, Hartwig

AU - Schlomm, Thorsten

AU - Steurer, Stefan

AU - Krech, Till

AU - Lebok, Patrick

N1 - © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2017/1

Y1 - 2017/1

N2 - DNA mismatch repair (MMR) is integral to the maintenance of genetic stability. We aimed to evaluate the clinical impact of MMR gene expression in prostate cancer. The MMR genes MSH6, MLH1 and PMS2 were analyzed by immunohistochemistry on a tissue microarray containing 11 152 prostate cancer specimens. Results were compared with ERG status and deletions of PTEN, 3p13, 5q21, and 6q15. MSH6, MLH1 and PMS2 expression was detectable in 89.5%, 85.4% and 85.0% of cancers, and was particularly strong in cancers with advanced pathological tumor stage (p<0.0001 each), high Gleason grade (p<0.0001 each), nodal metastasis (p≤0.0083), and early biochemical recurrence (p<0.0001). High levels of MMR gene expression paralleled features of genetic instability, such as the number of genomic deletions per cancer; strong expression of all three MMR genes was found in 24%, 29%, 30%, 33% and 42% of cancers with no, one, two, three or four to five deletions (p<0.0001). The prognostic value of the analyzed MMR genes was largely driven by the subset of cancers lacking ERG-fusion (p<0.0001), while the prognostic impact of MMR gene overexpression was only marginal in ERG-positive cancers. Multivariate analyses suggested an independent prognostic relevance of MMR genes in ERG-negative prostate cancers when compared to prognostic parameters available at the time of initial biopsy. In conclusion, MMR overexpression is common in prostate cancer, and is linked to poor outcome as well as features indicating genetic instability. ERG-fusion should be analyzed along with MMR gene expression in potential clinical tests.

AB - DNA mismatch repair (MMR) is integral to the maintenance of genetic stability. We aimed to evaluate the clinical impact of MMR gene expression in prostate cancer. The MMR genes MSH6, MLH1 and PMS2 were analyzed by immunohistochemistry on a tissue microarray containing 11 152 prostate cancer specimens. Results were compared with ERG status and deletions of PTEN, 3p13, 5q21, and 6q15. MSH6, MLH1 and PMS2 expression was detectable in 89.5%, 85.4% and 85.0% of cancers, and was particularly strong in cancers with advanced pathological tumor stage (p<0.0001 each), high Gleason grade (p<0.0001 each), nodal metastasis (p≤0.0083), and early biochemical recurrence (p<0.0001). High levels of MMR gene expression paralleled features of genetic instability, such as the number of genomic deletions per cancer; strong expression of all three MMR genes was found in 24%, 29%, 30%, 33% and 42% of cancers with no, one, two, three or four to five deletions (p<0.0001). The prognostic value of the analyzed MMR genes was largely driven by the subset of cancers lacking ERG-fusion (p<0.0001), while the prognostic impact of MMR gene overexpression was only marginal in ERG-positive cancers. Multivariate analyses suggested an independent prognostic relevance of MMR genes in ERG-negative prostate cancers when compared to prognostic parameters available at the time of initial biopsy. In conclusion, MMR overexpression is common in prostate cancer, and is linked to poor outcome as well as features indicating genetic instability. ERG-fusion should be analyzed along with MMR gene expression in potential clinical tests.

U2 - 10.1093/carcin/bgw116

DO - 10.1093/carcin/bgw116

M3 - SCORING: Journal article

C2 - 27803051

VL - 38

SP - 19

EP - 27

JO - CARCINOGENESIS

JF - CARCINOGENESIS

SN - 0143-3334

IS - 1

ER -