The tumor proliferation index marker Ki-67 is strongly associated with tumor cell proliferation, growth and progression, and is widely used in routine clinicopathological investigation. Prostate cancer is a complex multifaceted and biologically heterogeneous disease, and overtreatment of localized, low volume indolent tumors, is evident. Here, we aimed to assess Ki-67 expression and related outcomes of 535 patients treated with radical prostatectomy. The percentage of tumor epithelial cells expressing Ki-67 was determined by immunohistochemical assay, both digital image analysis and visual scoring by light microscope were used for quantification. The association of Ki-67 and prostate cancer was evaluated, as well as its prognostic value. There was a positive correlation between high expression of Ki-67 and Gleason score > 7 (p < 0.001) as well as tumor size (≥ 20 mm, p = 0.03). In univariate analyses, a high expression of Ki-67 in tumor epithelium was significantly associated with biochemical failure (BF) (digital scoring, p = 0.014) and (visual scoring, p = 0.004). In the multivariate analyses, a high level of Ki-67 was an independent poor prognostic factor for biochemical failure-free survival (BFFS) (Visual scoring, Ki67, p = 0.012, HR:1.50, CI95% 1.10–2.06). In conclusion, high Ki-67 expression is an independent negative prognostic marker for biochemical failure. Our findings support the role of Ki-67 as a significant, poor prognostic factor for in prostate cancer outcome.

BackgroundProstate cancer is a highly heterogeneous disease and one of the leading causes of mortality in developed countries. Specific prognostic and predictive markers for prostate cancer patients are still lacking. A causal relationship between androgens and the development of prostate cancer is generally considered biologically plausible, but androgens are not the sole effector in the complexity of prostate carcinogenesis. The aim of this study was to evaluate the prognostic significance of progesterone receptor in tumor tissue of T1-3N0 prostate cancer patients undergoing prostatectomy.MethodsTissue microarrays from 535 patients with prostate cancer were constructed. Duplicate cores of tumor cells and tumor stromal tissue from each resected specimen were extracted. Immunohistochemistry was used to evaluate the in-situ expression of progesterone receptor.ResultsIn univariate analyses, high tumor cell density (p = 0.006) and high tumor stromal cell density level (p = 0.045) of progesterone receptor were both significantly associated with tumor progression and clinical failure. In multivariate analysis, progesterone receptor expression in tumor cells was an independent negative prognostic factor for clinical failure (HR: 2.5, 95% CI: 1.2–5.2, p = 0.012).ConclusionHigh progesterone receptor density in tumor cells of the prostate cancer tumor is an independent negative prognostic factor for clinical failure.

Androgens are considered important in normal prostate physiology and prostate cancer (PCa) pathogenesis. However, androgen-targeted treatment preventing PCa recurrence is still lacking. This indicates additional mediators contributing to cancer development. We sought to determine the prognostic significance of estrogen receptors, ERα and -β, and the aromatase enzyme in PCa. Tissue microarrays were created from 535 PCa patients treated with radical prostatectomy. Expression of ERα, ERβ and aromatase were evaluated using immunohistochemistry. Representative tumor epithelial (TE) and tumor stromal (TS) areas were investigated separately. Survival analyses were used to evaluate the markers correlation to PCa outcome. In univariate analyses, ERα in TS was associated with delayed time to clinical failure (CF) (p = 0.042) and PCa death (p = 0.019), while ERβ was associated with reduced time to biochemical failure (BF) (p = 0.002). Aromatase in TS and TE was associated with increased time to BF and CF respectively (p = 0.016, p = 0.046). Multivariate analyses supported these observations, indicating an independent prognostic impact of all markers. When stratifying the analysis according to different surgical centers the results were unchanged. In conclusion, significant prognostic roles of ERα, ERβ and aromatase were discovered in the in PCa specimens of our large multicenter cohort.

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The role of steroid hormones in carcinogenesis of the prostate is to some extent unraveled thorough the effect of androgen deprivation therapy on prostate cancer (PCa) progression. Other members of the steroid hormone family, such as progesterone, are also implicated in PCa, but progesterone’s role remains undefined. This study aimed to examine the distribution of progesterone receptor isoforms (PGRA, PGRB) in PCa tissue and their association with clinical endpoints. This was conducted retrospectively by collecting radical prostatectomy specimens from 535 patients. Tissue was analyzed using tissue microarray, where representative tumor areas were carefully selected. Protein expression was evaluated through immunohistochemistry, in stromal and epithelial tissue. Associations between receptor expression and clinical data were considered using statistical survival analyses. Herein, we discovered a solely stromal PGRA- and a stromal and epithelial PGRB expression. Further, a high PGRB expression in tumor tissue was associated with an unfavorable prognosis in both univariate and multivariate analyses: Biochemical failure (HR: 2.0, 95% CI: 1.45–2.76, p < 0.001) and clinical failure (HR: 2.5, 95% CI: 1.29–4.85, p = 0.006). These findings are in agreement with our previous investigation on pan-PGR, indicating that the observed negative effect of PGR is represented by PGRB.