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FGD4 (Frabin) Overexpression in Pancreatic Neuroendocrine Neoplasms
Mohammad Shahid1, Tarra B George1, James Saller1
1From the Departments of Anatomic Pathology.
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.
Insights
Frabin is overexpressed in pancreatic neuroendocrine tumors (PNETs) and pancreatic neuroendocrine carcinomas (PECA). This finding suggests Frabin as a novel molecular alteration in these PNETs.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The pathogenesis of pancreatic neuroendocrine tumors (PNETs) remains incompletely understood.
- Frabin, a guanine nucleotide exchange factor, influences actin cytoskeleton dynamics crucial for cell migration, morphogenesis, polarization, and division.
Purpose of the Study:
- To investigate Frabin as a potential molecular alteration in PNETs.
- To assess Frabin expression in PNETs and pancreatic neuroendocrine carcinomas (PECA).
Main Methods:
- Immunohistochemistry and tissue microarray were used to evaluate Frabin expression in 29 PNET/PECA samples.
- Frabin immunostain was scored using the Allred system and correlated with tumor grade and stage.
- Statistical analysis included Spearman correlation coefficient and P values.
Main Results:
- Frabin was expressed in 82.7% (24/29) of the studied PNETs/PECAs, with cytoplasmic localization.
- A significant positive correlation was observed between Frabin immunohistochemistry score and tumor grade (ρ = 0.47, P = 0.01).
- No significant correlation was found between Frabin expression and tumor stage (P = 0.91).
Conclusions:
- Frabin overexpression represents a novel molecular alteration in PNETs and PECAs.
- Frabin expression correlates with the grade of pancreatic neuroendocrine tumors.
