# MSH2 loss in primary prostate cancer

Source: https://onco.cc/key-papers/paper-guedes-msh2-loss-primary-prostate-ccr-2017/  
OnCo record `paper-guedes-msh2-loss-primary-prostate-ccr-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Staining more than a thousand prostate tumours found the mismatch repair protein missing in about one in eighty, and twenty times more often in the highest-grade cancers.

## Summary

A total of 1,133 primary prostatic adenocarcinomas and 43 prostatic small cell carcinomas were screened by MSH2 immunohistochemistry with confirmation by next-generation sequencing, and microsatellite instability was assessed by PCR and by mSINGS. Of the primary adenocarcinomas and small cell carcinomas together, 14 of 1,176, 1.2%, had MSH2 loss. Eight per cent of adenocarcinomas with primary Gleason pattern 5 (Gleason score 9 to 10), 7 of 91, had MSH2 loss compared with 0.4%, 5 of 1,042, of tumours with any other score, and 2 of 43 small cell carcinomas, 5%. MSH2 loss was generally homogeneous, suggesting an early clonal event. Sequencing confirmed loss-of-function alterations in all 12 samples tested, with biallelic inactivation in 83% and hypermutation in 83%; 61% and 58% had definite microsatellite instability by PCR and mSINGS respectively, and 3 patients, 25%, had germline MSH2 mutations. Tumours with MSH2 loss had a higher density of infiltrating CD8-positive lymphocytes than grade-matched controls, 390 against 76 cells per square millimetre.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Clinical Cancer Research
- Year: 2017
- DOI: 10.1158/1078-0432.CCR-17-0955
- Authors: Guedes LB, Antonarakis ES, Schweizer MT, et al.
- Findings: MSH2 protein loss in 14 of 1,176 prostate carcinomas, 1.2%.; Eight per cent of primary Gleason pattern 5 tumours against 0.4% of all others.; Homogeneous loss, biallelic inactivation in 83% and hypermutation in 83% of sequenced cases.; Germline MSH2 mutation in 3 of 12 sequenced patients, 25%; CD8 density 390 against 76 cells per square millimetre.
- What it means: It gives a cheap way to find the rare men who could benefit from checkpoint blockade: an immunohistochemical stain on the highest-grade primary tumours, where the yield is twenty times higher than average. It also shows the loss is clonal and early, so the diagnostic block is an adequate place to look.
- Caveats: MSH2 immunohistochemistry alone, so tumours losing MLH1, MSH6 or PMS2 without MSH2 loss were not counted.; A single-institution series with retrospective case selection.; The immune infiltrate finding is descriptive and was not linked to treatment outcome here.

## Sources

- Guedes et al., Clin Cancer Res 2017: MSH2 loss by immunohistochemistry in 1,133 primary prostatic adenocarcinomas and 43 small-cell carcinomas: https://doi.org/10.1158/1078-0432.CCR-17-0955
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28790115/

## Connected records

- cancers: [Neuroendocrine and small-cell prostate cancer](https://onco.cc/cancers/prostate-nepc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)](https://onco.cc/targets/mmr/), [MSH2](https://onco.cc/targets/msh2/)
- pathways: [Mismatch repair & microsatellite instability](https://onco.cc/pathways/mismatch-repair-msi/), [The cancer-immunity cycle](https://onco.cc/pathways/cancer-immunity-cycle/)
- terms: [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Gleason score / Grade Group](https://onco.cc/terms/gleason-grade-group/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/), [Lynch syndrome](https://onco.cc/terms/lynch-syndrome/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)
- biomarkers: [dMMR (mismatch repair deficiency by IHC)](https://onco.cc/biomarkers/dmmr-ihc/), [MSI-high (microsatellite instability by PCR or sequencing)](https://onco.cc/biomarkers/msi-high/)

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