B. R. Herring1, C. MacVicar1, R. Guenter1, D. Dhall2, H. Chen1, G. Lee2, J. B. Rose1 1University Of Alabama at Birmingham, Surgery, Birmingham, Alabama, USA 2University Of Alabama at Birmingham, Pathology, Birmingham, Alabama, USA
Introduction: Immunogenic cell death (ICD) is often leveraged in immunotherapeutics. Calreticulin (CALR) is involved in the initiation of ICD, whereby upon sufficient insult to the cell it translocates from the endoplasmic reticulum to the plasma membrane and promotes phagocytosis of the damaged cell. Increased CALR portends improved outcomes for several cancers, but poor outcomes for others. However, no studies have examined the prognostic value of CALR for pancreatic neuroendocrine tumors (pNETs), which are often immunologically “cold.” Herein, we evaluate CALR as a prognostic biomarker for pNETs through immunohistochemistry (IHC) of tissue microarrays and retrospective chart review.
Methods: Following IHC of CALR, H-scoring was performed by a pathologist. Clinical variables analyzed included tumor grade, metastatic status (lymphatic and distant), and recurrence-free survival (RFS). 51 resected pNET samples were analyzed.
Results: CALR expression differed significantly between pNETs and normal pancreatic islets (p < 0.001), but not by tumor grade (p= 0.79), or either distant or lymph node metastatic status (p= 0.97; p= 0.09). CALR expression was not associated with tumor grade (p= 0.69), distant metastasis (p= 0.70), or lymph node metastasis (p= 0.40). However, CALR expression was positively associated with pNETs (compared to normal islets; p< 0.001). Furthermore, while there was a positive association between CALR expression and RFS, this relationship was not significant (p= 0.33).
Conclusion: While CALR expression is increased in pNETs, its influence on clinical outcomes remains unclear. Future studies will aim to examine these relationships in a larger cohort with more diverse clinical outcomes.