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FGD4 (Frabin) Overexpression in Pancreatic Neuroendocrine Neoplasms.

OBJECTIVE
The pathogenesis of pancreatic neuroendocrine tumors (PNETs) is still unclear. We propose Frabin as a new molecular alteration in PNETs. Frabin is a guanine nucleotide exchange factor playing a role in mediating actin cytoskeleton changes during cell migration, morphogenesis, polarization, and division.


METHODS
Patients with PNETs of different grades were assessed for Frabin expression using immunohistochemistry and tissue microarray. The tissue microarray included 12 grade 1 and 3 grade 2 PNETs and 14 grade 3 pancreatic neuroendocrine carcinomas (PECAs). Frabin immunostain was scored with Allred system. Statistical analysis used SAS and R software. Immunohistochemistry scores were correlated with tumor grade and stage. The Spearman correlation coefficient was calculated with P values.


RESULTS
Pancreatic neuroendocrine tumors were graded according to the World Health Organization 2017 guidelines. Frabin was expressed by 24 (82.7%) of the PNET/PECA studied. Only 5 (17.2%) of the 29 PNETs/PECA evaluated were Frabin negative. Frabin expression was cytoplasmic in all cases. We found a significant positive correlation (ρ = 0.47) between Frabin immunohistochemistry score and tumor grade (P = 0.01). No correlation was found between Frabin expression and tumor stage (P = 0.91).


CONCLUSIONS
We report Frabin overexpression as a novel molecular alteration occurring in PNETs/PECAs.