Study shows promise for PSA testing from fingerprick samples

Capillary blood samples (CBS) and venous samples are highly correlated, with negligible bias, for total prostate-specific antigen (TPSA), according to recent research (J Appl Lab Med 2025; 10.1093/jalm/jfae144). This finding helps pave the way for remote monitoring of prostate disease.

For many patients, including patients with frailty, older patients, and people with mental health issues or learning disabilities, the typical method of collecting blood from veins is unsuitable. CBS via a finger or heel prick may offer an alternative, especially for self-testing to monitor chronic conditions such as cancer.

Globally rising life expectancies and demographic changes portend more than a doubling in cases of prostate cancer by 2040, according to researchers. Previous research has shown CBS feasibility for testing biochemical analytes, but little evidence exists relating to the measurement of TPSA in CBS using modern routine methods.he researchers aimed to determine whether CBS via fingerprick was a viable and feasible alternative to using routine venous samples for testing TPSA concentrations in men.

The researchers tested 66 adult men ages 26−63 recruited from a urology clinic. Next, they collected samples via fingerprick using validated devices and venipuncture. Validated immunoassays for both the Roche cobas 801 and Beckman DXi platforms to measure TPSA were also used.

Across a range of normal concentrations to pathological ones, results between CBS and venous samples showed strong similarities. The average bias, 1.07%, was insignificant. Overall, the researchers saw no apparent proportional or constant bias.

Data showed that TPSA may be stable in samples tested with the Roche or Beckman assays and stored at ambient temperature for up to 8 days.

Calling the study a first step toward routine home TPSA testing, the authors called for more research first using standard methodology to examine the analytical accuracy of CBS for TPSA testing and then using CBS in a clinical setting.

Breast cancer gene variants of uncertain significance are newly classified

A new study of the crucial BRCA2 DNA-binding domain hotspot for pathogenic missense variants has led to the clinical classification of 91% of variants of uncertain significance (VUS) in this part of the gene (Nature 2025; doi: 10.1038/s41586-024-08388-8).

The researchers analyzed all possible single-nucleotide variants (SNVs) from exons 15-26 that encode the DNA-binding domain hotspot for pathogenic missense variants. CRISPR-Cas9 gene-editing technology was used to analyze the functional impact of 6,959 BRCA2 variants, definitively identifying those that increase cancer risk and those that do not. The researchers assigned variants to seven categories of pathogenicity. SNVs that encode loss-of-function missense variants were associated with increased risks of breast cancer and ovarian cancer.

For clinical classification of BRCA2 variants, the researchers also integrated functional assay results into models from ClinGen, the American College of Medical Genetics and Genomics, and the Association for Molecular Pathology.

These findings allow molecular labs and clinicians to give more precise, personalized care to patients with VUS in BRCA2. Labs can notify patients and clinicians about reclassified VUS, potentially altering care. Additionally, some breast, ovarian, pancreatic, or prostate cancer patients with the newly reclassified VUSs may benefit from targeted therapies such as poly ADP-ribose polymerase (PARP) inhibitors, which block activity of an enzyme that repairs damaged DNA.

The findings can be integrated with other datasets for the characterization and classification of all variants in this genetic location in individuals from all racial and ethnic backgrounds, and for all forms of cancer associated with BRCA2, the researchers noted.

Ovary removal and APOE4 allele may raise Alzheimer’s disease risk

Women who have had surgery to remove both ovaries before age 50 and carry the APOE4 allele are at high risk of developing Alzheimer’s disease (AD) late in life, recent research found (J Alzheimers Dis 2024; doi: 10.3233/JAD-240646).Because removing the ovaries results in immediate loss of estradiol and onset of menopause, the researchers examined prevalence and predictors of AD among a U.K. biobank cohort of 33,603 women ages 60 or older without AD who had early removal of both ovaries, and those who had natural menopause.

To determine AD, the researchers selected related ICD-9 and ICD-10 codes in medical records and used logistic regression to model the association between type of menopause with AD. Model predictors included age, education, age at menopause, use of hormone therapy, having the APOE4 variant, and history of cancer and smoking.

Women with early ovarian removal had four times the odds of developing AD (OR=4.12, 95% CI [2.02, 8.44]) compared with those who underwent natural menopause. Having the APOE4 variant (OR=4.29, 95% CI [2.43, 7.56]) and older age (OR=1.16, 95% CI [1.05, 1.28]) were associated with increased odds of AD in women who had ovaries removed and those who did not.

More years of education were associated with reduced odds of AD for women who had ovaries removed (OR=0.91, 95% CI [0.85, 0.98]) and those with natural menopause (OR=0.95, 95% CI [0.90, 0.99]). Hormone therapy use was associated with decreased odds of AD only for women who had ovaries removed (OR=0.43, 95% CI [0.23, 0.82]).

Researchers also found a modest relationship between body mass index and AD risk, but only for the women with early ovary removal. Each additional unit of BMI was associated with a 7% decrease in risk of developing Alzheimer's disease.

The study identifies women who had early removal of both ovaries and APOE4 as a likely at-risk group and demonstrates the importance of hormone therapy for lowering that risk. It also highlights the role of education in lowering risk of AD-associated cognitive decline in women with simultaneous menopause, the researchers wrote.