Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge

Table 1 Clinical hereditary diffuse gastric cancer testing criteria (from van der Post J Med Genet 2015[18])

Criteria include first and second degree relatives
Established criteria	2 GC cases regardless of age, at least one confirmed DGC
	One case of DGC < 40
	Personal or family history of DGC and LBC, one diagnosed < 50
Families in whom testing could be considered	Bilateral LBC or family history of 2 or more cases of LBC < 50
	Personal or familial history of cleftlip/palate in a patient with DGC
	In situ signet ring cell and/or pagetoid spread of signet ring cells

GC: Gastric cancer; DGC: Diffuse gastric cancer; LBC: Lobular breast cancer.

Table 2 Studies assessing prognosis of the signet-ring cell histotype in early gastric cancers

Ref.	Number of patients in study	Number of early gastric cancers	SRCC frequency in early gastric cancer	Prognosis of SRCC (type of analysis)
Maehara et al[57] (1992)	1500	384	7.3%	Similar (univariate)
Otsuji et al[58] (1998)	1498	568	19.8%	Better (univariate)
Hyung et al[80] (2002)	3104	933	28.2%	Better (univariate)
Kim et al[45] (2004)	2358	561	16.7%	Similar (multivariate)
Kunisaki et al[43] (2004)	1113	513	23.4%	Better (multivariate)
Ha et al[42] (2008)	1520	1520	25.5%	Better (univariate)
Jiang et al[44] (2011)	2315	269	20.1%	Better (multivariate)
Kwon et al[11] (2014)	769	326	15.6%	Better (multivariate)
Gronnier et al[46] (2013)	421	421	25%	Similar (multivariate)

SRCC: Signet-ring cell carcinoma.

Table 3 Studies assessing the prognosis of the signet-ring cell histotype in advanced gastric cancer

Ref.	Number of patients in study	Number of advanced gastric cancers	SRCC frequency in advanced gastric cancer	Median 5-yr survival of SRCC (vs non-SRCC)	P-value
Maehera et al[57] (1992)	1500	1116	2%	48% (vs 33%)	NS
Kim et al[53] (1994)	3702	NP	NP	32% (vs 45%)	< 0.05
Otsuji et al[58] (1998)	1498	630	9.5%	44% (vs 28%)	NS
Yokota et al[56] (1998)	923	NP	NP	11% (vs 38%)	NS
Theuer et al[59] (1999)	3020	NP	NP	NP	NS (multivariate)
Kim et al[45] (2004)	2358	1797	6%	35% (vs 40%)	NS
Kunisaki et al[43] (2004)	1113	600	9%	NP	NS
Li et al[42] (2007)	4759	4759	14%	42% (vs 51%)	0.009
Messager et al[68] (2011)	159	NP	NP	9% (vs 24%)	0.038
Taghavi et al[3] (2013)	12246	6261	26.3%	NP	NS (multivariate)
Jiang et al[44] (2011)	2315	2046	7%	31.5% (vs 35.7%)	NS
Kwon et al[11] (2014)	769	443	12.8%	26% vs 50.5%1	0.004
Zu et al[14] (2014)	741	741	5.9%	43.4% vs 87.1%2	0.0123
Heger et al[55] (2014)	723	312	33.5%	NP	0.02 (multivariate)

¹Ten-year survival;

²vs well-differentiated cancer;

³Comparison between all histotypes (well differentiated, moderately differentiated, poorly differentiated and SRCC). SRCC: Signet-ring cell carcinoma.

Table 4 Incidence of lymph node metastasis in early gastric cancer (according with Gotoda et al[81])

Depth of invasion	Tumor size	Grade of differentiation	Ulcerated versus not ulcerated tumor	Incidence of LNM	Recommended treatment
Mucosal	< 2 cm	Well differentiated	Not ulcerated	0%	EMR
		Poorly differentiated	Not ulcerated	0%	ESD (Asia)/surgery (Western)
		Well differentiated	Ulcerated	0%	ESD
		Poorly differentiated	Ulcerated	2%	Surgery
	2-3 cm	Well differentiated	Not ulcerated	0%	ESD
		Poorly differentiated	Not ulcerated	1.7%	Surgery
		Well differentiated	Ulcerated	0%	ESD
		Poorly differentiated	Ulcerated	2.4%	Surgery
	> 4 cm	Well differentiated		1.7%	Surgery
		Poorly differentiated		7.3%	Surgery
Submucosal (sm1)	< 3 cm	Well differentiated		5.6%	ESD/Surgery
		Poorly differentiated		NC	Surgery
	> 3 cm	Well differentiated		2.6%	Surgery
		Poorly differentiated		6.5%	Surgery
Submucosal (sm2)	< 3 cm	Well differentiated		19%	Surgery
		Poorly differentiated		NC	Surgery
	> 3 cm	Well differentiated		27%	Surgery
		Poorly differentiated		NC	Surgery

ESD: Endoscopic submucosal dissection.