ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Prevalence of Mismatch Repair Deficiency in Primary Prostate Cancer in a Large Prospective Cohort.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Genomic Determinants of Lethality and Therapeutic Vulnerability in Castration-Resistant Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
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17 authors.
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Abstract
purposeMismatch repair (MMR) deficiency and microsatellite instability are predictive biomarkers for immunotherapy response. The best approach to identify patients with such tumors is unclear in prostate cancer. EXPERIMENTAL
designThis study included 1,016 men diagnosed with primary prostate cancer during prospective follow-up of the Health Professionals Follow-up Study and Physicians' Health Study. The highest-grade/index lesions from radical prostatectomy (95%) or transurethral resections of the prostate were mounted on tissue microarrays. Scoring of immunohistochemistry for the MMR proteins MLH1, MSH2, MSH6, and PMS2 required a nontumor internal positive control for designating deficiency. Validation was done on full sections and with PCR-based quantification of microsatellite repeats.
resultsTumor stage was predominantly pathologically localized with a full distribution of Gleason scores. MMR tumor scoring could be performed with available internal positive control tissue in 75% to 90% of cases, depending on the MMR protein. Of the 903 tumors evaluable for MSH2 protein loss, 4 tumors had loss of MSH2 (prevalence, 0.4%; 95% confidence interval, 0.2%-1.1%), and 3 of 708 evaluable tumors had concomitant loss of MSH6 (prevalence, 0.4%; 95% confidence interval, 0.1%-1.2%). No tumor had loss of MLH1 or PMS2. The four MMR-deficient cases had higher Gleason scores, and three had non-zero microsatellite repeats.
conclusionsIn this nationwide prospective study, MMR deficiency was rare in primary, surgically treated prostate cancer. The low prevalence and the need for an internal positive control for this assay are feasibility concerns for unselected routine immunohistochemistry-based screening for MMR deficiency on limited tissue specimens, such as prostate biopsies.
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