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. 2019 Nov 18;19(2):499-506.
doi: 10.5114/aoms.2019.89773. eCollection 2023.

Expression differences between proteins responsible for DNA damage repair according to the Gleason grade as a new heterogeneity marker in prostate cancer

Damian Jaworski  1 , Arkadiusz Gzil  1 , Paulina Antosik  1 , Izabela Zarębska  1 , Joanna Dominiak  1 , Izabela Neska-Długosz  1 , Anna Kasperska  1 , Dariusz Grzanka  1 , Łukasz Szylberg  1   2
Affiliations

Expression differences between proteins responsible for DNA damage repair according to the Gleason grade as a new heterogeneity marker in prostate cancer

Damian Jaworski et al. Arch Med Sci. .

Abstract

Introduction: The purpose of this research was to explore the correlation between Gleason score and pattern and the expression of the MLH1, MSH2, MDC1, TP53BP1 proteins in prostate cancer (PC). Prostate cancer development is related to errors in DNA, among others double-strand breaks (DSB) and changes in the base sequence of the DNA. These errors should be repaired through mismatch (MMR) or DSB repair proteins such as MSH2, MLH1, MDC1 and TP53BP1.

Material and methods: A total of 500 prostate cancer specimens were recruited in this study. From among all gathered specimens the 52 most suitable cases were selected. The expression of examined proteins was detected by immunohistochemistry, and its correlation with the Gleason score and pattern were further analyzed through standard statistical algorithms.

Results: The results show a significant correlation between Gleason pattern and the nuclear expression of the MSH2 protein and the cytoplasmic expression of the MLH1 protein. Gleason score significantly correlates with the nuclear and the cytoplasmic expression of the MSH2 protein and the cytoplasmic expression of the MDC1 protein. There is no correlation between the nuclear or cytoplasmic expression of the TP53BP1 protein and Gleason pattern or score.

Conclusions: Our study suggests that the aberration in the MMR repair mechanism may be significantly more important regarding the grading among PC cells in comparison to the impact of alterations in the DSB repair mechanism. The lack of correlation between expression of the TP53BP1 protein and Gleason pattern and Gleason score suggests that the radiation resistance of PC is independent of alterations connected with TP53BP1.

Keywords: double-strand breaks; mismatch repair genes; radiotherapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Box plot of data with correlation between Gleason pattern and protein expression. A – Correlation between Gleason pattern and nuclear expression of MSH2 protein. B – Correlation between Gleason pattern and cytoplasmic expression of MLH1 protein
Figure 2
Figure 2
Box plot of data with the correlation between Gleason score and protein expression. A – Correlation between Gleason score and nuclear expression of MSH2 protein. B – Correlation between Gleason score and cytoplasmic expression of MSH2 protein. C – Correlation between Gleason score and cytoplasmic expression of MDC1 protein
Figure 3
Figure 3
Collage of representative area photographs with protein expression. A – Photograph of area with MSH2 protein expression. B – Photograph of area with MLH1 protein expression. C – Photograph of area with MDC1 protein expression. D – Photograph of area with TP53BP1 protein expression
See this image and copyright information in PMC

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