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01-05-2020 | Prostate Cancer | Original Article

High homogeneity of mismatch repair deficiency in advanced prostate cancer

Authors: Christoph Fraune, Ronald Simon, Doris Höflmayer, Katharina Möller, David Dum, Franziska Büscheck, Claudia Hube-Magg, Georgia Makrypidi-Fraune, Martina Kluth, Andrea Hinsch, Eike Burandt, Till Sebastian Clauditz, Waldemar Wilczak, Guido Sauter, Stefan Steurer

Published in: Virchows Archiv | Issue 5/2020

Abstract

Background

Recent reports have described favorable response rates for immune checkpoint inhibitors in prostate cancers with microsatellite instability (MSI). However, it is unclear whether MSI affects the entire tumor mass or is distributed heterogeneously, the latter potentially impairing treatment efficiency.

Methods

To identify prostate cancers with MSI, 316 advanced prostate cancers were analyzed by immunohistochemistry (IHC) for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6 on a TMA format.

Results

Out of 200 interpretable cancers, IHC findings were consistent with MSI in 10 tumors. In 9 of these 10 cancers, tissue blocks were available for subsequent large section IHC, confirming MSI in 6 cases, each with combined protein loss of MSH2 and MSH6. One additional tumor with unequivocal loss of MLH1 and PMS2 on the TMA, for which further analyses could not be carried out due to lack of tissue, was also considered to exhibit MSI. In total, 7 of 200 interpretable advanced prostate cancers were found to exhibit MMR deficiency/MSI (3.5%). Subsequent analysis of all available cancer-containing archived tissue blocks (n=114) revealed consistent and homogeneous MMR protein loss in each case. Polymerase chain reaction (PCR)-based analysis using the “Bethesda panel” could be executed in 6 MMR deficient tumors of which 4 were MSI-high and 2 were MSI-low.

Conclusions

The absence of intratumoral heterogeneity for the MMR status suggests that MSI occurs early in prostate cancer. It is concluded that MMR analysis on limited biopsy material by IHC is sufficient to estimate the MMR status of the entire cancer mass.

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Title: High homogeneity of mismatch repair deficiency in advanced prostate cancer
Authors: Christoph Fraune
Ronald Simon
Doris Höflmayer
Katharina Möller
David Dum
Franziska Büscheck
Claudia Hube-Magg
Georgia Makrypidi-Fraune
Martina Kluth
Andrea Hinsch
Eike Burandt
Till Sebastian Clauditz
Waldemar Wilczak
Guido Sauter
Stefan Steurer
Publication date: 01-05-2020
Publisher: Springer Berlin Heidelberg
Keywords: Prostate Cancer
Prostate Cancer
Polymerase Chain Reaction
Published in: Virchows Archiv / Issue 5/2020
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-019-02701-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

High homogeneity of mismatch repair deficiency in advanced prostate cancer

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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