Classification, clinicopathologic features and treatment of gastric neuroendocrine tumors

Table 1 Features of gastric neuroendocrine tumors

	Type I GNET	Type II GNET	Type III GNET	Type IV GNET
Proportion of GNETs	70%-80%	5%-6%	14%-25%	Rare
Tumor features	Usually multiple, small (1-2 cm), polypoid or intramucosal	Usually multiple, small (1-2 cm), polypoid	Single, large (> 2 cm, mean 5.1 cm)	Single, large (largest 16 cm)
Risk of metastases	2%-5%	10%-30%	50%-100%	100%
Tumor-related death	< 0.5%	< 5%	Well-differentiated: 25%-30%,poorly differentiated: 75%-87%	100% (Mean survival of 6.5-14.9 mo)
Proliferation (Ki67)	< 2%	< 2%	> 2%	> 30%
Immunohistochemistry	CgA, NSE, VMAT 2 positive	CgA positive	CgA negative	Synaptophysin, NSE, PGP9.5 positive;
				CgA negative
Histology	Mitoses (absent or occasionally)	mitoses < 1 per 2 HPFs	Mitoses > 1 per HPF	Severe grade 3 histology

GNET: Gastric neuroendocrine tumor; CgA: Chromogranin A; NSE: Neuron specific enolase; VMAT: Vesicular monoamine transporter; HPF: High power field.

Table 2 New tissue and serum tumor markers for specific diagnostics and prognostics of gastric neuroendocrine tumors

Ref.	Case	Hormones, amines and peptides for specific diagnostic and prognostics of GNETs	Expression
Giandomenico et al[42]	15	CD133	20% positive
Mia-Jan et al[43]	2	ISL1	Complete loss
Agaimy et al[44]	1	c-kit	Overexpression
Mori et al[45]	51	Cyclin E	Independent prognostic factor
		Cyclin E and P53	Prognostic relevance
Namikawa et al[41]	5	Chromogranin A	40% positive
		Synaptophysin	60% positive
		CD56	60% positive
		Neuron-specific enolase	40% positive
		p53 protein	100% positive

GNET: Gastric neuroendocrine tumor; ISL1: Islet-1.

Table 3 Summary of medical treatments for patients with gastric neuroendocrine tumors

	Type I GNET	Type II GNET	Type III GNET	Type IV GNET
Resection	Simple surveillance, endoscopic polypectomy, surgical excision associated with or without surgical antrectomy, total gastrectomy	Simple surveillance, endoscopic polypectomy, surgical excision associated with or without surgical antrectomy, total gastrectomy	Radical surgery	Radical surgery
Chemotherapy				Combination chemotherapy:Etoposide + cisplatin (CDDP)/carboplatin octreotide and pasireotide (SOM230);Somatosatin analogues;
				CDDP + CPT-11117Lu- and 90Y-labelled somatostatin analogues;Selective internal radiation therapy
Targeted radio therapy
Biological therapy	Interferon-α
Molecular targeted therapy	Inhibition of angiogenesis or molecular targeting of growth factor receptors, including sunitinib and imatinib

GNET: Gastric neuroendocrine tumor.