BackgroundMeasures of the expected genetic variability among full-sibs are of practical relevance, such as in the context of mating decisions. An important application field in animal and plant breeding is the selection and allocation of mates when large or small amounts of genetic variability among offspring are desired, depending on user-specific goals. Estimates of the Mendelian sampling variance can be obtained by simulating gametes from parents with known diplotypes. Knowledge of recombination rates and additive marker effects is also required. In this study, we aimed at developing an exact method that can account for both additive and dominance effects.ResultsWe derived parent-specific covariance matrices that exactly quantify the within-family (co-)variability of additive and dominance marker effects. These matrices incorporate prior knowledge of the parental diplotypes and recombination rates. When combined with additive marker effects, they allow the exact derivation of the Mendelian sampling (co-)variances of (estimated) breeding values for several traits, as well for the aggregate genotype. A comparative analysis demonstrated good average agreement between the exact values and the simulation results for a practical dataset (74,353 German Holstein cattle).ConclusionsThe newly derived method is suitable for calculating the exact amount of intra-family variation of the estimated breeding values and genetic values (comprising additive and dominance effects).

To assess the prognostic and diagnostic utility of PSA immunostaining, tissue microarrays containing 17,747 prostate cancers, 3,442 other tumors from 82 different (sub) types and 608 normal tissues were analyzed at two different antibody concentrations (1:100 and 1:800). In normal tissues, PSA expression was limited to prostate epithelial cells. In prostate cancers, PSA staining was seen in 99.9–100% (1:800–1:100) primary tumors, 98.7–99.7% of advanced recurrent cancers, in 84.6–91.4% castration resistant cancers, and in 7.7–18.8% of 16 small cell carcinomas. Among extraprostatic tumors, PSA stained positive in 0–3 (1:800-1:100) of 19 osteosarcomas, 1-2 of 34 ovarian cancers, 0-2 of 35 malignant mesotheliomas, 0–1 of 21 thyroid gland carcinomas and 0–1 of 26 large cell lung cancers. Reduced staining intensity and loss of apical staining were strongly linked to unfavorable tumor phenotype and poor prognosis (p < 0.0001 each). This was all the more the case if a combined “PSA pattern score” was built from staining intensity and pattern. The prognostic impact of the “PSA pattern score” was independent of established pre- and postoperative clinico-pathological prognostic features. In conclusion, PSA immunostaining is a strong prognostic parameter in prostate cancer and has high specificity for prostate cancer at a wide range of antibody dilutions.

B7-H3 is a member of the B7 superfamily of immune checkpoint molecules. B7-H3 up regulation has been linked to cancer development and progression in many tumors including prostate cancer. To clarify the potential utility of B7-H3 as a prognostic biomarker, B7-H3 expression was analyzed by immunohistochemistry in more than 17 000 prostate cancers. Normal prostatic glands were largely B7-H3 negative, while membranous B7-H3 immunostaining was seen in 47.0% of analyzed cancers. B7-H3 immunostaining was weak in 12.3%, moderate in 21.1% and strong in 13.5% of cases. High B7-H3 expression was associated with pT, Gleason score, lymph node metastasis, high Ki67 labeling index and early prostate-specific antigen recurrence (P < 0.0001 each). High B7-H3 expression was also linked to high androgen receptor expression and TMPRSS2:V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusions (P < 0.0001 each). Multivariate analyses showed a strong independent prognostic impact of high B7-H3 expression in all cancers and in the ERG negative subgroup. Comparison with previously analyzed frequent chromosomal deletions revealed a close association with Phosphatase and Tensin Homolog deletions. Analysis of B7-H3, alone or in combination with other markers, might be of clinical utility, especially in the subgroup of ERG negative prostate cancers.