Low Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression

Abstract

Tumor-to-stroma ratio (TSR) is a prognostic factor that expresses the relative amounts of tumor and intratumoral stroma. In this study, its clinical and molecular relevance was evaluated in prostate cancer (PCa). The feasibility of automated quantification was tested in digital scans of tissue microarrays containing 128 primary tumors from 72 PCa patients stained immunohistochemically for epithelial cell adhesion molecule (EpCAM), followed by validation in a cohort of 310 primary tumors from 209 PCa patients. In order to investigate the gene expression differences between tumors with low and high TSR, we applied multigene expression analysis (nCounter® PanCancer Progression Panel, NanoString) of 42 tissue samples. TSR scores were categorized into low (<1 TSR) and high (≥1 TSR). In the pilot cohort, 31 patients (43.1%) were categorized as low and 41 (56.9%) as high TSR score, whereas 48 (23.0%) patients from the validation cohort were classified as low TSR and 161 (77.0%) as high. In both cohorts, high TSR appeared to indicate the shorter time to biochemical recurrence in PCa patients (Log-rank test, p = 0.04 and p = 0.01 for the pilot and validation cohort, respectively). Additionally, in the multivariate analysis of the validation cohort, TSR predicted BR independent of other factors, i.e., pT, pN, and age (p = 0.04, HR 2.75, 95%CI 1.07–7.03). Our data revealed that tumors categorized into low and high TSR score show differential expression of various genes; the genes upregulated in tumors with low TSR score were mostly associated with extracellular matrix and cell adhesion regulation. Taken together, this study shows that high stroma content can play a protective role in PCa. Automatic EpCAM-based quantification of TSR might improve prognostication in personalized medicine for PCa.

Pauperization of Emerin from nuclear envelope during chromatin bridge resolution drives prostate cancer cell migration and invasiveness

“…A total of 351 primary tumor samples corresponding to 117 d’Amico intermediate to high PCa patients, who underwent radical prostatectomy in the Department of Urology at the Medical University of Gdańsk (Poland) in years 2018–2022, were analyzed. Tumor specimens were prepared as tumor microarrays (TMAs) that consisted of 3 tumor fragments per patient, including fragments of tumor with highest and dominant Gleason score (Nastały et al , 2021). All the tissue cores were assessed by experienced pathologist for the percentage of tumor cells.…”

“…Analysis of differentially expressed genes in relation to EMD status was prepared and performed as described (Nastały et al , 2021). Briefly, total mRNA was extracted from 69 samples prepared as formalin-fixed paraffin-embedded (FFPE) primary prostate tumor tissue cores (three 20 µm-thick, unstained FFPE sections per patient) using the Rneasy Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer’s protocol.…”

Correlation of Intravoxel Incoherent Motion and Diffusion Kurtosis MR Imaging Models With Reactive Stromal Grade in Prostate Cancer

“…The RSG was classified into four grades 20 : grade 3 (51%–100% reactive stroma or a ratio of at least 1:1 between gland and stroma), grade 2 (16%–50% reactive stroma), grade 1 (6%–15% reactive stroma) or grade 0 (0%–5% reactive stroma). Then, patients were divided into high RSG PCa (>50% reactive stroma) and low RSG PCa (≤50% reactive stroma) groups 21 . The four different RSGs are shown in Fig.…”

“…Then, patients were divided into high RSG PCa (>50% reactive stroma) and low RSG PCa (≤50% reactive stroma) groups. 21 The four different RSGs are shown in Fig. 3.…”

Pauperization of Emerin from nuclear envelope during chromatin bridge resolution drives prostate cancer cell migration and invasiveness

“…A total of 351 primary tumor samples corresponding to 117 d'Amico intermediate to high PCa patients, who underwent radical prostatectomy in the Department of Urology at the Medical University of Gdańsk (Poland) in years 2018-2022, were analyzed. Tumor specimens were prepared as tumor microarrays (TMAs) that consisted of 3 tumor fragments per patient, including fragments of tumor with highest and dominant Gleason score (50). All the tissue cores were assessed by experienced pathologist for the percentage of tumor cells.…”