MRI-Derived Apparent Diffusion Coefficient of Peri-Prostatic Adipose Tissue Is a Potential Determinant of Prostate Cancer Aggressiveness in Preoperative Setting: A Preliminary Report.

Background: The aim of this study was to test the association between periprostatic adipose tissue (PPAT)­apparent diffusion coefficient (ADC) value recorded at multiparametric magnetic resonance imaging (mpMRI) and determinants of prostate cancer (PCa) aggressiveness in the preoperative setting. Methods: Data from 219 consecutive patients undergoing prostate biopsy (PBx) for suspicion of PCa, between January 2020 and June 2022, at our institution were retrospectively evaluated. Only patients who had mpMRI performed before PBx were included. The distribution of demographics and clinical features among PPAT-ADC values up to vs. above the median was studied using both parametric and non-parametric tests, according to variables. Linear and logistic regression models tested the association between PPAT-ADC values and determinants of PCa aggressiveness and the presence of intermediate-high risk PCa, respectively. Results: Of 132 included patients, 76 (58%) had PCa. Median PPAT-ADC was 876 (interquartile range: 654 − 1112) × 10−6 mm2/s. Patients with PPAT-ADC up to the median had a higher rate of PIRADS (Prostate Imaging­Reporting and Data System) 5 lesions (41% vs. 23%, p = 0.032), a higher percentage of PBx positive cores (25% vs. 6%, p = 0.049) and more frequently harbored ISUP (International Society of Urological Pathology) > 1 PCa (50% vs. 28%, p = 0.048). At univariable linear regression analyses, prostate-specific antigen (PSA), PSA density, PIRADS 5, and percentage of PBx positive cores were associated with lower PPAT-ADC values. PPAT-ADC up to the median was an independent predictor for intermediate-high risk PCa (odds ratio: 3.24, 95%CI: 1.17−9.46, p = 0.026) after adjustment for age and body mass index. Conclusions: Lower PPAT-ADC values may be associated with higher biopsy ISUP grade group PCa and a higher percentage of PBx-positive cores. Higher-level studies are needed to confirm these preliminary results.

The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions.

Little is known about the immunoediting process in precancerous lesions. We explored this aspect of benign colorectal adenomas with a descriptive analysis of the immune pathways and immune cells whose regulation is linked to the morphology and size of these lesions. Two series of polypoid and nonpolypoid colorectal adenomas were used in this study: 1) 84 samples (42 lesions, each with matched samples of normal mucosa) whose gene expression data were used to quantify the tumor morphology- and size-related dysregulation of immune pathways collected in the Molecular Signature Database, using Gene Set Enrichment Analysis; 2) 40 other lesions examined with immunohistochemistry to quantify the presence of immune cells in the stromal compartment. In the analysis of transcriptomic data, 429 immune pathways displayed significant differential regulation in neoplasms of different morphology and size. Most pathways were significantly upregulated or downregulated in polypoid lesions versus nonpolypoid lesions (regardless of size). Differential pathway regulation associated with lesion size was observed only in polypoid neoplasms. These findings were mirrored by tissue immunostaining with CD4, CD8, FOXP3, MHC-I, CD68, and CD163 antibodies: stromal immune cell counts (mainly T lymphocytes and macrophages) were significantly higher in polypoid lesions. Certain markers displayed significant size-related differences regardless of lesion morphology. Multivariate analysis of variance showed that the marker panel clearly discriminated between precancerous lesions of different morphologies and sizes. Statistical analysis of immunostained cell counts fully support the results of the transcriptomic data analysis: the density of infiltration of most immune cells in the stroma of polypoid precancerous lesions was significantly higher than that observed in nonpolypoid lesions. Large neoplasms also have more immune cells in their stroma than small lesions. Immunoediting in precancerous colorectal tumors may vary with lesion morphology and stage of development, and this variability could influence a given lesion's trajectory to cancer.