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Somatostatin and chemokine CXCR4 receptor expression in pancreatic adenocarcinoma relative to pancreatic neuroendocrine tumours

  • Original Article – Cancer Research
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Abstract

Purpose

Pancreatic adenocarcinoma (PAC) represents one of the most fatal types of cancer with an exceptionally poor prognosis, underscoring the need for improved diagnostic and treatment approaches. An over-expression of somatostatin receptors (SST) as well as of the chemokine receptor CXCR4 has been shown for many tumour entities. Respective expression data for PAC, however, are scarce and contradictory.

Methods

Overall, 137 tumour samples from 70 patients, 26 of whom were diagnosed with PAC and 44 with pancreatic neuroendocrine tumour (PanNET), were compared in terms of SST and CXCR4 expression by immunohistochemical analysis using well-characterized rabbit monoclonal antibodies.

Results

Only SST1 and CXCR4 expression was detected in PAC tumours, with SST1 present in 42.3% and CXCR4 in 7.7% of cases. However, the overall staining intensity was very weak. In contrast to the tumour cells, in many PAC cases, tumour capillaries exhibited strong SST3, SST5, or CXCR4 expression. In PanNETs, SST2 was the most-prominently expressed receptor, observed in 75.0% of the tumours at medium–strong intensity. SST5, SST1, and CXCR4 expression was detected in 20.5%, 15.9%, and 11.4% of PanNET cases, respectively, but the staining intensity was only weak. SST2 positivity in PanNET, but not in PAC, was associated with favourable patient outcomes.

Conclusions

SST or CXCR4 expression in PAC is clearly of no therapeutic relevance. However, indirect targeting of these tumours via SST3, SST5, or CXCR4 on tumour microvessels may represent a promising additional therapeutic strategy.

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Abbreviations

CXCR4:

CXC motif chemokine receptor 4

GEP-NEC:

Gastroenteropancreatic neuroendocrine carcinomas

GEP-NET:

Gastroenteropancreatic neuroendocrine tumours

IRS:

Immunoreactivity score

PAC:

Pancreatic adenocarcinoma

PanNET:

Pancreatic neuroendocrine tumour

SST:

Somatostatin receptor

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Funding

The Theranostic Research Center, Zentralklinik Bad Berka, 99437 Bad Berka, Germany, provided funding for this research.

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Author notes

  1. Ylberta Kajtazi and Daniel Kaemmerer have contributed equally to the first authorship.

Authors and Affiliations

  1. Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, 07747, Jena, Germany

    Ylberta Kajtazi, Stefan Schulz & Amelie Lupp

  2. Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany

    Daniel Kaemmerer

  3. Laboratory of Pathology and Cytology Bad Berka, Bad Berka, Germany

    Jörg Sänger

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  1. Ylberta Kajtazi
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  2. Daniel Kaemmerer
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  4. Stefan Schulz
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  5. Amelie Lupp
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Contributions

Conceived and designed the experiments: Daniel Kaemmerer and Amelie Lupp. Provided the tumour samples: Jörg Sänger. Provided the antibodies: Stefan Schulz. Acquired the clinical data: Daniel Kaemmerer. Performed the experiments: Ylberta Kajtazi and Amelie Lupp. Analysed the data: Ylberta Kajtazi and Amelie Lupp. Interpreted the data: Amelie Lupp. Wrote the paper: Amelie Lupp. Critically revised the manuscript: Ylberta Kajtazi, Daniel Kaemmerer, Jörg Sänger, Stefan Schulz, and Amelie Lupp. Each of the authors has approved the manuscript and acknowledges that he or she participated sufficiently in the work to take public responsibility for its content.

Corresponding author

Correspondence to Amelie Lupp.

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Conflict of interest

Daniel Kaemmerer received funding and support for travel to meetings from IPSEN and PFIZER. All other authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Permission was gained from the local ethics committee (Ethikkommission der Landesärztekammer Thüringen) for this retrospective analysis. For this type of study, formal consent was not required. All data were recorded and analysed anonymously.

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Kajtazi, Y., Kaemmerer, D., Sänger, J. et al. Somatostatin and chemokine CXCR4 receptor expression in pancreatic adenocarcinoma relative to pancreatic neuroendocrine tumours. J Cancer Res Clin Oncol 145, 2481–2493 (2019). https://doi.org/10.1007/s00432-019-03011-0

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