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Endocrine Abstracts (2023) 98 B23 | DOI: 10.1530/endoabs.98.B23

NANETS2023 Basic Science (28 abstracts)

Calreticulin is associated with clinical characteristics in pancreatic neuroendocrine tumors

Brendon Herring 1 , Caroline Macvicar 1 , Rachael Guenter 1 , Weisheng Chen 2 , Isra Elhussin 2 , Clayton Yates 2 , Deepti Dhall 3 , Herbert Chen 2 , Goo Lee 2 & J. Bart Rose 1


1Department of Surgery, University of Alabama at Birmingham, Birmingham, AL; 2Department of Pathology, University of Alabama at Birmingham, Birmingham, AL; 3Department of Biology, Tuskegee University, Tuskegee, AL


Background: Following IHC of CALR, H-scoring was performed by a pathologist. H-scoring was validated by MIF of the same tissue, wherein random-forest machine learning (ML) classifiers were employed to classify cells. ML classifiers were trained to distinguish between pNET cells and tumor stroma using approximately 30% of cells for the respective cell population of interest in each TMA core. Pearson’s correlations were used to evaluate the relationship between H-scoring and mean fluorescent intensity in tumor cells. H-scoring was then evaluated for a relationship with clinical variables, including tumor grade and metastatic status (both lymphatic and distant). 111 resected pNET samples were analyzed.

Methods: CALR MIF was performed for 40/89 patients. CALR H-scoring and IF were highly correlated (r= 71 [95% CI 50-83]; p < 0.0001). CALR expression was significantly higher in pNETs compared to normal pancreatic islets (p < 0.0001), as well as in primary pNETs compared to distant metastatic pNETs (P =0.02). There was however no difference in CALR expression based on tumor grade (0.82) or N stage (0.58).

Results: CALR MIF was performed for 40/111 patients. CALR H-scoring and IF were highly correlated (r= 71 [95% CI 50-83]; p < 0.0001). CALR expression differed significantly between pNETs and normal pancreatic islets (p < 0.0001), approached significance by N stage (P =0.07), but did not differ by M stage (P =0.72) or tumor grade (P =0.78).

Table Germline P/LPV in G3NENs [Note: ** not sequenced in tumor]
CALR H Score (mean ± sd) p value
Tumor/IsletTumor (n =111) 217±95Islet(n =17) 53±51 < 0.0001*
GradeG1 (n =51) 213±101G2 (n =52) 218±92G3 (n =6) 241±730.82
M StageM0 (n =63) 232±86M1 (n =38) 186±105Mx (n =10)0.02*
N StageN0 (n =62) 219±96N1 (n =26) 232±85Nx (n =23)0.58

Conclusion: CALR expression is increased in pNETs compared to normal islets and may be decreased in cases of distant metastatic disease. Future studies will aim to examine these relationships in a larger cohort with more diverse clinical outcome to better define this relationship.

Abstract ID 23717

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