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Updated: Dec 22, 2025
An Orthotopic Resectional Mouse Model of Pancreatic Cancer
Published on: September 24, 2020
Histopathological and Immunophenotypic Changes of Pancreatic Neuroendocrine Tumors after Neoadjuvant Peptide Receptor
Marco Schiavo Lena1, Stefano Partelli2,3, Paola Castelli4
1Pathology Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy. schiavolena.marco@hsr.it.
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.
Insights
Neoadjuvant Peptide Receptor Radionuclide Therapy (PRRT) for pancreatic neuroendocrine tumors (PanNETs) increased stromal content and M2 macrophages. SSTR2A expression was largely retained, with no impact on progression-free survival observed in this study.
Area of Science:
- Oncology
- Nuclear Medicine
- Pathology
Background:
- Peptide Receptor Radionuclide Therapy (PRRT) is an emerging treatment for pancreatic neuroendocrine tumors (PanNETs).
- The use of PRRT as a neoadjuvant therapy and its effects on tumor histopathology are not well-understood.
- Characterizing PRRT-induced changes is crucial for optimizing its role in PanNET management.
Purpose of the Study:
- To evaluate the histopathological and immunophenotypic changes induced by neoadjuvant PRRT in PanNETs.
- To compare these changes with upfront surgery in a matched cohort.
- To assess the potential impact of neoadjuvant PRRT on tumor characteristics and SSTR2A expression.
Main Methods:
- Retrospective analysis of 24 patients who received neoadjuvant PRRT for PanNETs, matched with 24 patients who had upfront surgery.
- Comprehensive morphological and immunohistochemical evaluation of tumor samples.
- Analysis included stromal percentage, SSTR2A expression, and CD163+ M2-polarized macrophage density and morphology.
Main Results:
- Neoadjuvant PRRT significantly increased the total percentage of stroma compared to upfront surgery (p < 0.0001).
- SSTR2A expression was retained in 87% of patients post-PRRT.
- Increased density of CD163+ M2-polarized macrophages was observed in the PRRT group (p = 0.022), with a tendency towards epithelioid morphology (p = 0.043).
Conclusions:
- Neoadjuvant PRRT in PanNETs is associated with reduced tumor diameter, increased stroma, and preserved SSTR2A expression.
- PRRT leads to an increased density of M2-polarized macrophages, suggesting an altered tumor microenvironment.
- No histological parameters evaluated were associated with progression-free survival in the neoadjuvant PRRT group.
