PDGFRα expression as a novel therapeutic marker in well-differentiated neuroendocrine tumors

Aims: To evaluate the biological significance of dense vascular networks associated with low-grade NENs, we assessed the impact of PDGFR alpha tissue expression in 77 GEP/NEN patients, associating PDGFR alpha expression with the morphological characterization in low-grade tumors. Methods and results: Paraffin-embedded specimens of 77 GEP- NEN tissues, collected from January 2006 to March 2018, were evaluated for PDGFR alpha tissue expression and correlations with clinicopathological characteristics. PDGFR alpha tissue expression was significantly correlated with grade and the NEN growth pattern (p < 0.001) but not with gender, primary site or lymph nodes metastatic status. PDGFR alpha staining was mainly localized in the vascular pole of the neuroendocrine cells and in Enterochromaffin (EC) cells. In particular PDGFR alpha tissue expression was significantly more expressed in G2 (p < 0.001) than G1 and G3 cases (p 0.004; p < 0.0002;) and correlated with an insular growth pattern. PDGFR alpha tissue expression was associated with the Ki67 index and we found a significant negative trend of association with the Ki67 proliferation index (P < 0.001): thus PDGFR alpha expression is referred to morphological and not to proliferative data. Conclusions: PDGFR alpha represents an effective target for new anti-angiogenic treatment in WD- GEP-NENs, in particular in G2 cases, and in G3 cases only when there is a mixed insular-acinar pattern. In this context, it is important to carefully delineate those tumors that might better respond to this type of treatment alone or in combination. Further investigation of the relationship between PD-L1 and PDGFRa is warranted, and may contribute to optimize the therapeutic approach in patients with GEP-NENs.