Neuropilin-2 is an independent prognostic factor for shorter cancer-specific survival in patients with acinar adenocarcinoma of the prostate

Angelika Borkowetz, Michael Froehner, Martina Rauner, Stefanie Conrad, Kati Erdmann, Thomas Mayr, Kaustubh Datta, Lorenz C. Hofbauer, Gustavo B. Baretton, Manfred Wirth, Susanne Fuessel, Marietta Toma, Michael H. Muders

Research output: Contribution to journalArticle

Abstract

Neuropilin-2 (NRP2) is a member of the neuropilin receptor family and known to regulate autophagy and mTORC2 signaling in prostate cancer (PCa). Our study investigated the association of immunohistochemical NRP2 expression with clinicopathological data in PCa patients. For this purpose, we generated a tissue microarray with prostate tissue specimens from 400 PCa patients treated by radical prostatectomy. We focused on patients with high-risk factors such as extraprostatic extension (pT ≥ 3), Gleason score ≥8 and/or the presence of regional lymph node metastases (pN1). Protein levels of NRP2, the vascular endothelial growth factor C (VEGFC) and oncogenic v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) gene as an indicator for TMPRSS2-ERG fusion was assessed in relation to the patients' outcome. NRP2 emerged as an independent prognostic factor for cancer-specific survival (CSS) (hazard ratio 2.360, 95% confidence interval = 1.2–4.8; p = 0.016). Moreover, the association between NRP2 expression and shorter CSS was also especially pronounced in patients at high risk for progression (log-rank test: p = 0.010). We evaluated the association between NRP2 and the TMPRSS2-ERG gene fusion status assessed by immunohistochemical nuclear ERG staining. However, ERG staining alone did not show any prognostic significance. NRP2 immunostaining is significantly associated with shorter CSS in ERG-negative tumors (log-rank test: p = 0.012). No prognostic impact of NRP2 expression on CSS was observed in ERG-positive tumors (log-rank test: p = 0.153). Our study identifies NRP2 as an important prognostic marker for a worse clinical outcome especially in patients with a high-risk PCa and in patients with ERG-negative PCa.

Original languageEnglish (US)
JournalInternational Journal of Cancer
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Neuropilin-2
Prostate
Adenocarcinoma
Survival
Prostatic Neoplasms
Neoplasms
Neuropilins
Alpharetrovirus
Staining and Labeling
Vascular Endothelial Growth Factor C
Neoplasm Grading
Gene Fusion
Autophagy
Prostatectomy
Oncogenes
Lymph Nodes

Keywords

  • ERG
  • VEGFC
  • neuropilin-2
  • prognosis
  • prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Neuropilin-2 is an independent prognostic factor for shorter cancer-specific survival in patients with acinar adenocarcinoma of the prostate. / Borkowetz, Angelika; Froehner, Michael; Rauner, Martina; Conrad, Stefanie; Erdmann, Kati; Mayr, Thomas; Datta, Kaustubh; Hofbauer, Lorenz C.; Baretton, Gustavo B.; Wirth, Manfred; Fuessel, Susanne; Toma, Marietta; Muders, Michael H.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Borkowetz, A, Froehner, M, Rauner, M, Conrad, S, Erdmann, K, Mayr, T, Datta, K, Hofbauer, LC, Baretton, GB, Wirth, M, Fuessel, S, Toma, M & Muders, MH 2019, 'Neuropilin-2 is an independent prognostic factor for shorter cancer-specific survival in patients with acinar adenocarcinoma of the prostate', International Journal of Cancer. https://doi.org/10.1002/ijc.32679
Borkowetz, Angelika ; Froehner, Michael ; Rauner, Martina ; Conrad, Stefanie ; Erdmann, Kati ; Mayr, Thomas ; Datta, Kaustubh ; Hofbauer, Lorenz C. ; Baretton, Gustavo B. ; Wirth, Manfred ; Fuessel, Susanne ; Toma, Marietta ; Muders, Michael H. / Neuropilin-2 is an independent prognostic factor for shorter cancer-specific survival in patients with acinar adenocarcinoma of the prostate. In: International Journal of Cancer. 2019.
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abstract = "Neuropilin-2 (NRP2) is a member of the neuropilin receptor family and known to regulate autophagy and mTORC2 signaling in prostate cancer (PCa). Our study investigated the association of immunohistochemical NRP2 expression with clinicopathological data in PCa patients. For this purpose, we generated a tissue microarray with prostate tissue specimens from 400 PCa patients treated by radical prostatectomy. We focused on patients with high-risk factors such as extraprostatic extension (pT ≥ 3), Gleason score ≥8 and/or the presence of regional lymph node metastases (pN1). Protein levels of NRP2, the vascular endothelial growth factor C (VEGFC) and oncogenic v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) gene as an indicator for TMPRSS2-ERG fusion was assessed in relation to the patients' outcome. NRP2 emerged as an independent prognostic factor for cancer-specific survival (CSS) (hazard ratio 2.360, 95{\%} confidence interval = 1.2–4.8; p = 0.016). Moreover, the association between NRP2 expression and shorter CSS was also especially pronounced in patients at high risk for progression (log-rank test: p = 0.010). We evaluated the association between NRP2 and the TMPRSS2-ERG gene fusion status assessed by immunohistochemical nuclear ERG staining. However, ERG staining alone did not show any prognostic significance. NRP2 immunostaining is significantly associated with shorter CSS in ERG-negative tumors (log-rank test: p = 0.012). No prognostic impact of NRP2 expression on CSS was observed in ERG-positive tumors (log-rank test: p = 0.153). Our study identifies NRP2 as an important prognostic marker for a worse clinical outcome especially in patients with a high-risk PCa and in patients with ERG-negative PCa.",
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AU - Froehner, Michael

AU - Rauner, Martina

AU - Conrad, Stefanie

AU - Erdmann, Kati

AU - Mayr, Thomas

AU - Datta, Kaustubh

AU - Hofbauer, Lorenz C.

AU - Baretton, Gustavo B.

AU - Wirth, Manfred

AU - Fuessel, Susanne

AU - Toma, Marietta

AU - Muders, Michael H.

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