FGD4 (Frabin) Overexpression in Pancreatic Neuroendocrine Neoplasms

Abstract

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.

Polymorphism of FGD4 and Myelosuppression in Patients with Esophageal Squamous Cell Carcinoma

“…FGD4 has been widely studied in the congenital peripheral neuropathy Charcot-Marie-Tooth Type 4 [24,25]. In a small number of cancer studies, such as those involving pancreatic neuroendocrine neoplasm and prostate cancer, FGD4 was found to function in tumor development and progression and as a chemosensitizer [26][27][28]. In prostate cancer, a study by Bossan et al illustrated that knockdown of FGD4 decreased cell proliferation and migration, and that suppression of its expression improved sensitivity to docetaxel, and the potential mechnism pathways and cell processes were under investigation [26].…”

A genome-wide screen in mice to identify cell-extrinsic regulators of pulmonary metastatic colonisation

“…FDG4, also known as FRABIN, contains an actin filament-binding domain (ABD), an Dbl homology domain (DHD), a cysteine rich-domain (CRD), and two pleckstrin homology domains (PHD), which are involved in binding to the actin and activating CDC42 at that vicinity, resulting in actin cytoskeleton reorganization (allowing for shape changes such as the formation of filopodia and lamellipodia) (Nakanishi and Takai 2008). FGD4 overexpression has been observed in pancreatic neuroendocrine neoplasms (Shahid et al 2019) and expression of FDG4 positively correlates with the aggressive phenotype of prostate cancer (Bossan et al 2018). Mutations in this gene can cause Charcot-Marie-Tooth (CMT) disease type 4H (CMT4H), characterised by heterogeneous hereditary motor and sensory neuropathies as a result of demyelination of peripheral nerves (Delague et al 2007).…”

TROP-2, Nectin-4, GPNMB, and B7-H3 Are Potentially Therapeutic Targets for Anaplastic Thyroid Carcinoma

“…A total of 54 patients with ATC who were treated at Kanagawa Cancer Center from 1990 to 2009 were enrolled in this study. The study design was approved by the Ethics Committee of the Kanagawa Cancer Center (approval number, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34].…”