Comparing the expression profiles of steroid hormone receptors and stromal cell markers in prostate cancer at different Gleason scores

Abstract

The recent developments in anti-angiogenic and immunomodulatory drugs show that the tumour micro-environment (TME) becomes increasingly important in cancer research. Here we investigated the correlation between the Gleason score (GS) and the TME by comparing tissue expression profiles of steroid hormone receptors, cancer activated fibroblast (CAF) markers and vessel densities between different GS groups. Therefore, matched patient cohorts were composed for different GS (6-7-8). Tissue micro-arrays with 6 samples/patient were processed for immunohistochemistry. Stained slides were digitised, stroma and epithelium were selectively annotated, and all selected areas were quantitatively analysed for marker expression. The most striking findings were decreased stromal expression levels of several steroid hormone receptors, increased CAF-phenotypes and increased vessel densities in high GS prostate cancer compared to low GS prostate cancer and paired prostate non-tumour tissue. The present data reveal a complex correlation between prostate cancer differentiation and TME components and suggest that different GS can be associated with different possible actionable targets in the TME. The use of standardised digital image analysis tools generated robust and reproducible quantitative data, which is novel and more informative compared to the classic semi-quantitative and observer-dependent visual scoring of immunohistochemistry.

The potential of tumour microenvironment markers to stratify the risk of recurrence in prostate cancer patients

“…From the 24 patients with CLR, 14 showed distant metastasis, 9 showed local recurrence and 1 presented with both. Patient cohorts were partially overlapping with cohorts described previously [19] and were matched for Grade groups (GG), lymph node-status, margin-status, p-stage and age (see Table 1 for clinicopathological parameters). All cases were revised for correct ISUP GG by an experienced urogenital pathologist (TG) and only GS7 (ISUP GG2 / GG3) cases without tertiary component were included.…”

“…Some parts of the methods described below are identical to those used in a previous study [19]. Identical parts apply to the design of the tissue micro-arrays (TMA), immunohistochemistry and data analysis methodology.…”

“…IHC stains were performed on the Leica Bond-Max system (Leica Microsystems, Belgium). The automated staining procedure was identical as described previously [19].…”

“…Previously, we investigated the relation between different GS and the expression of several TME cell markers [19]. This panel included the vascular marker CD31, CAF markers (CD34, caveolin-1 (CAV-1) and alpha smooth muscle actin (αSMA)) and steroid hormone receptors (SHR: androgen receptor (AR), progesterone receptor (PR) and estrogen receptor alpha (ERα)) in paired prostate non-tumour (PNT) and PCa tissue.…”

Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy

“…As previously mentioned, increasing evidence suggests that PCa-derived CAFs secretome is modulated by AR signaling (Yu et al, 2013;Cioni et al, 2018). Interestingly, AR expression by CAFs evolves during PCa progression (Olapade-Olaopa et al, 1999;Gevaert et al, 2018). Indeed, metastatic PCa and castration resistance PCa display significantly lower stromal AR expression than localize tumor-and androgen-dependent PCa (Li et al, 2008;Singh et al, 2014).…”