MSH2-deficient prostate tumours have a distinct immune response and clinical outcome compared to MSH2-deficient colorectal or endometrial cancer.
Prostate Cancer Prostatic Dis
; 24(4): 1167-1180, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34108644
ABSTRACT
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 ANDRESULTS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Neoplasias Colorretais
/
Neoplasias do Endométrio
/
Proteína 2 Homóloga a MutS
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Prostate Cancer Prostatic Dis
Assunto da revista:
ENDOCRINOLOGIA
/
NEOPLASIAS
/
UROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Austrália