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Histopathological and Immunophenotypic Changes of Pancreatic Neuroendocrine Tumors after Neoadjuvant Peptide Receptor Radionuclide Therapy (PRRT)

Endocrine Pathology volume 31, pages 119–131 (2020)Cite this article

Abstract

Peptide Receptor Radionuclide Therapy (PRRT) is an emerging therapeutic option for pancreatic neuroendocrine tumors (PanNETs). A possible role for PRRT as a neoadjuvant agent is still largely undetermined, explored only in case reports or small case series. Likewise, the histopathological and immunophenotypic changes induced by PRRT are poorly characterized. In the present study, 24 patients who underwent neoadjuvant PRRT on the basis of their disease’s characteristics were retrospectively matched with 24 patients who underwent upfront surgery. A comprehensive morphological and immunohistochemical evaluation was conducted to identify the differences in the two groups. The most significant findings were that the total percentage of stroma increased significantly in patients who underwent PRRT (p < 0.0001) and the characteristics of the stroma were different in the two groups. The somatostatin receptors type 2A (SSTR2A) were retained in most patients (87%) after PRRT. The density of CD163+ M2-polarized macrophages was greater in the PRRT group (p = 0.022), and M2-polarized macrophages tended to assume an epithelioid morphology (p = 0.043). In the neoadjuvant PRRT group, none of the histological parameters considered were associated with progression-free survival (PFS). Neoadjuvant PRRT in PanNETs is associated with reduced tumor diameter, an increased percentage of stroma, preserved SSTR2A expression in most of the cases, and an increased CD163+ M2-polarized macrophages density.

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Acknowledgments

The authors want to thank Francesca Di Salvo for statistical analysis, Roberto Cairella and Graziella Santambrogio for their invaluable technical assistance.

Valentina Andreasi PhD studentship was supported by Gioja Bianca Costanza legacy donation.

Author information

Affiliations

  1. Pathology Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy

    Marco Schiavo Lena, Chanel Elisha Smart & Claudio Doglioni

  2. Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Stefano Partelli, Valentina Andreasi & Massimo Falconi

  3. Vita e Salute University, Milan, Italy

    Stefano Partelli, Massimo Falconi & Claudio Doglioni

  4. Department of Pathology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy

    Paola Castelli & Giuseppe Zamboni

  5. Department of Pathology, European Institute of Oncology, Milan, Italy

    Eleonora Pisa

  6. Nuclear Medicine Department, Sant’Anna Hospital, Ferrara, Italy

    Mirco Bartolomei

  7. Division of Gastrointestinal Surgery, European Institute of Oncology, Milan, Italy

    Emilio Bertani

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  1. Marco Schiavo Lena
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  2. Stefano Partelli
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Correspondence to Marco Schiavo Lena.

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The Authors have disclosed that they have no significant relationship with, or financial interest in, any commercial companies pertaining to this article.

The study was conducted according to the criteria set by the 1964 Declaration of Helsinki and later Amendments. Due to the retrospective nature of the study, approval by the ethical committee was waived.

No identifying details of the patients were mentioned in this study, all information were anonymized, and the images included may not identified persons.

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Schiavo Lena, M., Partelli, S., Castelli, P. et al. Histopathological and Immunophenotypic Changes of Pancreatic Neuroendocrine Tumors after Neoadjuvant Peptide Receptor Radionuclide Therapy (PRRT). Endocr Pathol 31, 119–131 (2020). https://doi.org/10.1007/s12022-020-09623-4

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Keywords

  • Pancreatic neuroendocrine tumor
  • Peptide Receptor Radionuclide Therapy
  • M2-polarized macrophages
  • Immunohistochemistry
  • Response to neoadjuvant therapy