Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Mar;71(3):313-316.
doi: 10.1016/j.eururo.2016.06.018. Epub 2016 Jun 22.

Expression of STAT3 in Prostate Cancer Metastases

Affiliations
Free PMC article

Expression of STAT3 in Prostate Cancer Metastases

Nicholas Don-Doncow et al. Eur Urol. .
Free PMC article

Abstract

STAT3 and its upstream activator IL6R have been implicated in the progression of prostate cancer and are possible future therapeutic targets. We analyzed 223 metastatic samples from rapid autopsies of 71 patients who had died of castration-resistant prostate cancer (CRPC) to study protein and gene expression of pSTAT3 and IL6R. Immunohistochemical analysis revealed that 95% of metastases were positive for pSTAT3 and IL6R, with varying expression levels. Bone metastases showed significantly higher expression of both pSTAT3 and IL6R in comparison to lymph node and visceral metastases. STAT3 mRNA levels were significantly higher in bone than in lymph node and visceral metastases, whereas no significant difference in IL6R mRNA expression was observed. Our study strongly supports the suggested view of targeting STAT3 as a therapeutic option in patients with metastatic CRPC.

Patient summary: We studied the levels of two proteins (pSTAT3 and IL6R) in metastases from patients who died from castration-resistant prostate cancer. We found high levels of pSTAT3and IL6R in bone metastases, suggesting that these proteins could be used as targets for new anticancer drugs.

Keywords: Castration-resistant; Metastases; Prostate cancer; STAT3; Tissue microarray.

Conflict of interest statement

Financial disclosures: Anders Bjartell certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Anders Bjartell and Rebecka Hellsten are shareholders of Glactone Pharma AB. The remaining authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
– Examples of immunohistochemical (IHC) staining and distribution of IHC expression scores for pSTAT3 and IL6R. (A–D) Examples of pSTAT3 staining in metastases. (A) Negative (0) liver staining. (B) Low (1) lymph node staining. (C) Medium (2) lymph node staining. (D) High (3) bone staining. (E–H) Examples of IL6R staining in metastases. (E) Negative (0) liver staining. (F) Low (1) lymph node staining. (G) Medium (2) lymph node staining. (H) High (3) bone staining. Scale bar, 100 µm. (I– L) Expression in bone compared to lymph node and visceral metastases. (I) Overall tissue sample distribution for pSTAT3 staining, with significant differences observed between bone (n = 113), lymph node (n = 51), and visceral (n = 51) metastases. (J) Matched tissue samples for pSTAT3 staining (n = 24), with significant differences observed between bone and both lymph node and visceral metastases. (K) Overall tissue samples for IL6R staining, with significant differences observed only between bone (n = 117) and lymph node (n=50) metastases, and no significant difference between bone and visceral metastases (n = 50). (L) Matched tissue samples for IL6R staining (n = 23), with significant differences observed between bone and both lymph node and visceral metastases. (I,J) Scoring index: zero = 0; low = 1, 2; medium = 3, 4; high = 5–9. (K,L) Scoring index: zero = 0; low = 1; medium = 2; high = 3. Asterisks denote significant differences between groups according to a Wilcoxon signed-rank test (** p ≤ 0.01, *** p ≤ 0.001).
Fig. 2
Fig. 2
Comparison of mRNA expression scores (log2 signal intensity of Cy3) for bone, lymph node, and visceral metastases. Asterisks denote significant differences between groups according to a Wilcoxon signed-rank test (*** p ≤ 0.001). Significant differences in STAT3 levels were observed between bone and both lymph node and visceral metastases. No significant differences were observed in IL6R expression between the different metastasis sites.

Comment in

Similar articles

See all similar articles

Cited by 17 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback