MSH2-deficient prostate tumours have a distinct immune response and clinical outcome compared to MSH2-deficient colorectal or endometrial cancer
- McCoy, P; Mangiola, S; Macintyre, G; Hutchinson, R; Tran, B; Pope, B; Georgeson, P; Hong, MKH; Kurganovs, N; Lunke, S; Clarkson, MJ; Cmero, M; Kerger, M; Stuchbery, R; Chow, K; Haviv, I; Ryan, A; Costello, AJ; Corcoran, NM; Hovens, CM;
- Journal Title
- Prostate Cancer and Prostatic Diseases
- Publication Type
- epub ahead of print
- BACKGROUND: Recent publications have shown patients with defects in the DNA mismatch repair (MMR) pathway driven by either MSH2 or MSH6 loss experience a significant increase in the incidence of prostate cancer. Moreover, this increased incidence of prostate cancer is accompanied by rapid disease progression and poor clinical outcomes. METHODS AND RESULTS: We show that androgen-receptor activation, a key driver of prostate carcinogenesis, can disrupt the MSH2 gene in prostate cancer. We screened tumours from two cohorts (recurrent/non-recurrent) of prostate cancer patients to confirm the loss of MSH2 protein expression and identified decreased MSH2 expression in recurrent cases. Stratifying the independent TCGA prostate cancer cohort for MSH2/6 expression revealed that patients with lower levels of MSH2/6 had significant worse outcomes, in contrast, endometrial and colorectal cancer patients with lower MSH2/6 levels. MMRd endometrial and colorectal tumours showed the expected increase in mutational burden, microsatellite instability and enhanced immune cell mobilisation but this was not evident in prostate tumours. CONCLUSIONS: We have shown that loss or reduced levels of MSH2/MSH6 protein in prostate cancer is associated with poor outcome. However, our data indicate that this is not associated with a statistically significant increase in mutational burden, microsatellite instability or immune cell mobilisation in a cohort of primary prostate cancers.
- WEHI Research Division(s)
- Bioinformatics; Personalised Oncology
- PubMed ID
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-06-21 10:26:02Last Modified: 2021-06-21 10:44:58