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Expression of tSTAT3, pSTAT3 727 , and pSTAT3 705 in the epithelial cells of hormone-naïve prostate cancer

Krzyzanowska, Agnieszka LU ; Don-Doncow, Nicholas LU ; Marginean, Felicia Elena LU orcid ; Gaber, Alexander LU ; Watson, R. William ; Hellsten, Rebecka LU and Bjartell, Anders LU (2019) In Prostate 79(7). p.784-797
Abstract


Background: The signal transducer and activator of transcription 3 (STAT3) pathway is observed to be constitutively activated in several malignancies including prostate cancer (PCa). In the present study, we investigated the expression of total STAT3 (tSTAT3) and two forms of activated phosphorylated STAT3 (pSTAT3
727
and pSTAT3
705
) in tissue microarrays (TMA) of two cohorts of localized hormone-naïve PCa... (More)


Background: The signal transducer and activator of transcription 3 (STAT3) pathway is observed to be constitutively activated in several malignancies including prostate cancer (PCa). In the present study, we investigated the expression of total STAT3 (tSTAT3) and two forms of activated phosphorylated STAT3 (pSTAT3
727
and pSTAT3
705
) in tissue microarrays (TMA) of two cohorts of localized hormone-naïve PCa patients and analyzed associations between the expression and disease outcome. Methods: The expression of tSTAT3, pSTAT3
727
, and pSTAT3
705
was scored in the nuclei and cytoplasm of prostatic gland epithelial cells in two TMAs of paraffin-embedded prostatic tissue. The TMAs consisted of tissue originated from hormone-naïve radical prostatectomy patients from two different sites: Malmö, Sweden (n = 300) and Dublin, Ireland (n = 99). Results: The nuclear expression levels of tSTAT3, pSTAT3
727
, and pSTAT3
705
in the epithelial cells of benign glands were significantly higher than in the cancerous glands. Cytoplasmic tSTAT3 levels were also higher in benign glands. Patients with low pSTAT3
727
and pSTAT3
705
levels in the cancerous glands showed reduced times to biochemical recurrence, compared with those with higher levels. No significant trends in nuclear nor in cytoplasmic tSTAT3 were observed in relation to biochemical recurrence in the Malmö cohort. Higher cytoplasmic tSTAT3 was associated with reduced time to biochemical recurrence in the Dublin cohort. Adding the tSTAT3 and pSTAT3 expression data to Gleason score or pathological T stage did not improve their prognostic values. Conclusions: Low pSTAT3
727
and pSTAT3
705
expression in epithelial cells of cancerous prostatic glands in hormone-naïve PCa was associated with faster disease progression. However, pSTAT3 and tSTAT3 expression did not improve the prognostic value of Gleason score or pathological T stage and may not be a good biomarker in the early hormone naïve stages of PCa.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biomarker, immunohistochemistry, prostate cancer, signal transducer and activator of transcription 3, tissue microarray
in
Prostate
volume
79
issue
7
pages
784 - 797
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85063292004
  • pmid:30905090
ISSN
0270-4137
DOI
10.1002/pros.23787
language
English
LU publication?
yes
id
f37a7b2e-4d22-4867-9ab4-52ec64266bed
date added to LUP
2019-04-02 12:23:38
date last changed
2024-03-02 23:38:17
@article{f37a7b2e-4d22-4867-9ab4-52ec64266bed,
  abstract     = {{<p><br>
                                                         Background: The signal transducer and activator of transcription 3 (STAT3) pathway is observed to be constitutively activated in several malignancies including prostate cancer (PCa). In the present study, we investigated the expression of total STAT3 (tSTAT3) and two forms of activated phosphorylated STAT3 (pSTAT3                             <br>
                            <sup>727</sup><br>
                                                          and pSTAT3                             <br>
                            <sup>705</sup><br>
                                                         ) in tissue microarrays (TMA) of two cohorts of localized hormone-naïve PCa patients and analyzed associations between the expression and disease outcome. Methods: The expression of tSTAT3, pSTAT3                             <br>
                            <sup>727</sup><br>
                                                         , and pSTAT3                             <br>
                            <sup>705</sup><br>
                                                          was scored in the nuclei and cytoplasm of prostatic gland epithelial cells in two TMAs of paraffin-embedded prostatic tissue. The TMAs consisted of tissue originated from hormone-naïve radical prostatectomy patients from two different sites: Malmö, Sweden (n = 300) and Dublin, Ireland (n = 99). Results: The nuclear expression levels of tSTAT3, pSTAT3                             <br>
                            <sup>727</sup><br>
                                                         , and pSTAT3                             <br>
                            <sup>705</sup><br>
                                                          in the epithelial cells of benign glands were significantly higher than in the cancerous glands. Cytoplasmic tSTAT3 levels were also higher in benign glands. Patients with low pSTAT3                             <br>
                            <sup>727</sup><br>
                                                          and pSTAT3                             <br>
                            <sup>705</sup><br>
                                                          levels in the cancerous glands showed reduced times to biochemical recurrence, compared with those with higher levels. No significant trends in nuclear nor in cytoplasmic tSTAT3 were observed in relation to biochemical recurrence in the Malmö cohort. Higher cytoplasmic tSTAT3 was associated with reduced time to biochemical recurrence in the Dublin cohort. Adding the tSTAT3 and pSTAT3 expression data to Gleason score or pathological T stage did not improve their prognostic values. Conclusions: Low pSTAT3                             <br>
                            <sup>727</sup><br>
                                                          and pSTAT3                             <br>
                            <sup>705</sup><br>
                                                          expression in epithelial cells of cancerous prostatic glands in hormone-naïve PCa was associated with faster disease progression. However, pSTAT3 and tSTAT3 expression did not improve the prognostic value of Gleason score or pathological T stage and may not be a good biomarker in the early hormone naïve stages of PCa.                         <br>
                        </p>}},
  author       = {{Krzyzanowska, Agnieszka and Don-Doncow, Nicholas and Marginean, Felicia Elena and Gaber, Alexander and Watson, R. William and Hellsten, Rebecka and Bjartell, Anders}},
  issn         = {{0270-4137}},
  keywords     = {{biomarker; immunohistochemistry; prostate cancer; signal transducer and activator of transcription 3; tissue microarray}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{7}},
  pages        = {{784--797}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Prostate}},
  title        = {{Expression of tSTAT3, pSTAT3                         
                        <sup>727</sup>
                                                 , and pSTAT3                          
                        <sup>705</sup>
                                                  in the epithelial cells of hormone-naïve prostate cancer}},
  url          = {{http://dx.doi.org/10.1002/pros.23787}},
  doi          = {{10.1002/pros.23787}},
  volume       = {{79}},
  year         = {{2019}},
}