Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Low levels of phosphorylated epidermal growth factor receptor in nonmalignant and malignant prostate tissue predict favorable outcome in prostate cancer patients.
Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
Visa övriga samt affilieringar
2010 (Engelska)Ingår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 16, nr 4, s. 1245-1255Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

PURPOSE: To explore if the expression of phosphorylated epidermal growth factor receptor (pEGFR) in nonmalignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients. EXPERIMENTAL DESIGN: We used formalin-fixed tissues obtained through the transurethral resection of the prostate from 259 patients diagnosed with prostate cancer after the transurethral resection of the prostate, and patients were then followed with watchful waiting. Tissue microarrays of nonmalignant and malignant prostate tissue were stained with an antibody against pEGFR. The staining pattern was scored and related to clinicopathologic parameters and to outcome. RESULTS: Low phosphorylation of EGFR in prostate epithelial cells, both in the tumor and surprisingly also in the surrounding nonmalignant tissue, was associated with significantly longer cancer-specific survival in prostate cancer patients. This association remained significant when Gleason score and local tumor stage were added together with pEGFR to a Cox regression model. Tumor epithelial pEGFR immunoreactivity was significantly correlated to tumor cell proliferation, tumor vascular density, and nonmalignant epithelial pEGFR immunoreactivity. Patients with metastases had significantly higher immunoreactivity for tumor and nonmalignant epithelial pEGFR compared with patients without metastases. CONCLUSIONS: Low pEGFR immunoreactivity is associated with the favorable prognosis in prostate cancer patients and may provide information about which patients with Gleason score 6 and 7 tumors that will survive their disease even without treatment. Changes in the nonmalignant tissue adjacent to prostate tumors give prognostic information.

Ort, förlag, år, upplaga, sidor
2010. Vol. 16, nr 4, s. 1245-1255
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:umu:diva-32701DOI: 10.1158/1078-0432.CCR-09-0103ISI: 000278545200018PubMedID: 20145160OAI: oai:DiVA.org:umu-32701DiVA, id: diva2:305200
Tillgänglig från: 2010-03-22 Skapad: 2010-03-22 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
Ingår i avhandling
1. Androgen controlled regulatory systems in prostate cancer: potential new therapeutic targets and prognostic markers
Öppna denna publikation i ny flik eller fönster >>Androgen controlled regulatory systems in prostate cancer: potential new therapeutic targets and prognostic markers
2008 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

BACKGROUND: Prostate cancer is by far the most common cancer among Swedish men. Some patients have an aggressive lethal disease, but the majority of affected men have long expected survival. Unfortunately, the diagnostic tools available are insufficient in predicting disease aggressiveness. Novel prognostic markers are therefore urgently needed. Furthermore, metastatic prostate cancer is generally treated with castration, but the long-term effects are insufficient. Additional studies are therefore needed to explore how the effects of this therapy can be enhanced. Prostate growth and regression is beside testosterone controlled by locally produced regulators. Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) are two of the major regulators in the normal prostate and in prostate tumours.

MATERIALS AND METHODS: VEGF and EGFR were explored in the prostate, by treating rats with either anti-VEGF or anti-EGFR treatment during castration and testosterone-stimulated prostate growth. Rats with implanted androgen-independent prostate tumours were treated with an inhibitor of both VEGF receptor-2 (VEGFR-2) and EGFR. Stereological techniques, immunohistochemistry, western blotting and quantitative real-time PCR were used to evaluate these experiments. Furthermore, prostate tissue from untreated prostate cancer patients was used to retrospectively explore the expression of phosphorylated-EGFR (pEGFR) in relation to outcome.

RESULTS: Anti-VEGF treatment during testosterone-stimulated prostate growth, inhibited vascular and prostate growth. Anti-EGFR treatment during castration and testosterone-stimulated prostate growth resulted in enhanced castration effects and inhibited prostate growth. Anti-vascular treatment of androgen-independent prostate cancer with an inhibitor of VEGFR-2 and EGFR, that targets the normal and tumour vasculature, enhanced the effects of castration. Low immunoreactivity for pEGFR in prostate epithelial cells, both in the tumour and also in the surrounding non-malignant tissue, was associated with good prognosis.

CONCLUSIONS: Anti-vascular treatment, with an inhibitor of VEGFR-2 and EGFR, in combination with castration could be an effective way to treat androgen-insensitive prostate tumours. VEGF and EGFR signalling are necessary components in testosterone-stimulated prostate growth. Phosphorylation of EGFR could be a useful prognostic marker for prostate cancer patients. Tumours may affect the surrounding non-malignant tissue and pEGFR immunoreactivity in the morphologically normal prostate tissue can be used to retrieve prognostic information.

Ort, förlag, år, upplaga, sidor
Umeå: Medicinsk biovetenskap, 2008. s. 56
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1230
Nyckelord
prostate cancer, angiogenesis, human biopsy, androgen ablation, castration, prognostic marker, prognostic factor, growth control, VEGF, vascular endothelial growth factor, EGFR, epidermal growth factor receptor, pEGFR, phosphorylated EGFR, phosphorylated epidermal growth factor receptor
Nationell ämneskategori
Patobiologi
Identifikatorer
urn:nbn:se:umu:diva-1930 (URN)978-91-7264-698-8 (ISBN)
Disputation
2008-12-10, Hörsal Betula, 6M, Norrlands universitetssjukhus, 901 85 Umeå, Umeå, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2008-11-24 Skapad: 2008-11-24 Senast uppdaterad: 2010-03-24Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltextPubMed

Sök vidare i DiVA

Av författaren/redaktören
Hammarsten, PeterKaralija, AmarJosefsson, AndreasRudolfsson, Stina HäggströmWikström, PernillaStattin, PärBergh, Anders
Av organisationen
PatologiUrologi och andrologi
I samma tidskrift
Clinical Cancer Research
Medicin och hälsovetenskap

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 282 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf