Poorly cohesive cells gastric carcinoma including signet-ring cell cancer: Updated review of definition, classification and therapeutic management

Table 1 Subcategories of poorly cohesive cell carcinoma as proposed by the Verona consensus[16] in two recent clinical studies[47,48]

Ref.	Category of PCC
	SRC type: > 90% of Signet Ring cells	PCC with SRC component: < 90% but > 10% of SRC	PCC-NOS: < 10% of SRC
Bencivenga et al[47]	32 (18.5)	98 (56.6)	43 (24.9)
Roviello et al[48]	0 (0)	87 (60.8)	56 (39.2)

PCC: Poorly cohesive cell; SRC: Signet ring cells; NOS: Not otherwise specified.

Table 2 Concordance rates between World Health Organization and Laurén classification systems

Ref.	Reclassification of SRC and PCC-GC according to Laurén classification
	n	% Intestinal	% Diffuse	% Mixed
Pyo et al[7], 2016	3170	0.6	96.3	3.1
Pyo et al[173], 2017	5309	0.0	96.1	3.9
Wanebo et al[174],1993	187	2	87	11
Hass et al[175], 2011	160	7.6	66.2	26.2
Lee et al[176], 2012	320	0.0	90.6	9.4
Heger et al[58], 2014	235	0.0	75.3	20.0
Chon et al[53], 2017	1646	1.2	96.4	2.4

SRC: Signet ring cells; PCC: Poorly cohesive cells; GC: Gastric cancer.

Table 3 Summary of studies reporting the all-stage prognostic value of signet ring cell- and poorly cohesive cell-gastric cancer

Ref.	n		n SRC-CG (%)		% LNM		5-yr survival rate %, SR-CGC vs other	Univariate	Multivariate	Compared to
Eastern studies
Maehara et al[49], 1992	1500		51 (3.4)		33.3		74.5 vs 52.4	P < 0.01	-	Non SRC-GC
Kim et al[177], 1994	3702		450 (12.2)		50.6		59.7 vs 57.7/48.6/43.1	NS	-	WD/MD/PD
Otsuji et al[178], 1998	1498		154 (10.3)		27.9		68.2 vs 43.9 (10-yr survival rate)	P < 0.05	-	Non SRC-GC
Yokota et al[179], 1998	923		93 (10.1)		43		Worse	NS	-	Non SRC-GC
Kim et al[180], 2004	2358		204 (8.7)		26.5		60.2 vs 48.9	P < 0.01	NS	Non SRC-GC
Park et al[181], 2008	2275		251 (11.0)		46.2		66.2 vs 66.7/54.5/51.0	WD: NS; PD/MC: P < 0.001	P = 0.002a	WD/PD/MC
Zhang et al[45], 2010	1439		218 (15.1)		76.1		44.9 vs 36	P = 0.013	NS	Non SRC-GC
Chiu et al[182], 2011	2439		505 (20.7)		53.7		57.6 vs 56	NS	-	Non SRC-GC
Jiang et al[55], 2011	1439		211 (14.7)		52,0		49.8 vs 41.4	P = 0.001	-	Non SRC-GC
Lee et al[176], 2012	1002		320 (31.9)		37.2		84.8 vs 71.9/57.8	P < 0.001	NS	PD/MC
Kwon et al[50], 2014	769		108 (14.0)		43.5		55.4 vs 64.5/46.2 (10-yr survival rate)	P < 0.001	NS	WD-MD/PD-MC
Liu et al[162], 2015	1464		138 (9.4)		30.4		36.2 vs 49.5	P < 0.001	P < 0.001	Non SRC-GC
Chon et al[53], 2017	7667		1646 (21.5)		25.8		80.0 vs 70.0 (10-y survival rate)	P < 0.001	NS	WMD/PD
Lu et al[183], 2016	2199		354 (16.1)		-		15.9 mo vs 22.1 mo	P = 0.002	< 0.001	Non SRC-GC
Western studies
Theuer et al[184], 1999	3020	453 (15.0)		NR		Similar		NS	NS	Non SRC-GC
Piessen et al[35], 2009	180	59 (32.8)		83.1		28 vs 46		P = 0.004	P = 0.004	Non SRC-GC
Taghavi et al[44], 2012	10246	2666 (26)		59.7		Similar (Disease-specific survival)		NS	P = 0.15	Non SRC-GC
Bamboat et al[51], 2014	569	210 (36.9)		61.0		49 vs 24/43 (5-y cumulative-mortality)		P < 0.0001	-	WMD/PD
Postlewait et al[6], 2015	768	312 (40.6)		66.3		33.7 mo vs 46.6 mo (OS)		P = 0.011	NS	Non SRC-GC
Voron et al[8], 2016	1799	899 (50)		73.2		26 mo vs 51 mo (median survival)		P < 0.001	P < 0.041	Non SRC-GC

^aThe survival rate of patients with stage IV signet ring cells-gastric cancer was poorer than those with the other three types.

LNM: Lymph node metastasis; SRC-GC: Signet ring cells-gastric cancer; non SRC-GC: gastric cancer other types than SRC-GC; WMD: Well-and moderately-differentiated gastric cancer; PD: Poorly differentiated; MC: Mucinous cancer; NS: Non-significant.

Table 4 Summary of studies reporting prognostic value of signet ring cell- and poorly cohesive cell-early gastric cancer

Ref.	n	n SRC-GC (%)	% LNM	5-yr survival rate %, SRC-GC vs other	Univariate	Multivariate	Compared to
Eastern studies
Maehara et al[49], 1992	384	28 (7.3)	10.7	100 vs 94.8	NS	-	Non SRC-GC
Kim et al[177], 1994	785	185 (23.6)	7.6	92.9 vs 83.9/87.3/93.6	NS	-	WD/MD/PD
Otsuji et al[178], 1998	568	94 (16.5)	5.3	93 vs 76.3	P < 0.05	-	Non SRC-GC
Yokota et al[179], 1998	253	41 (16.2)	-	Similar	NS	-	Non SRC-GC
Hyung et al[80], 2002	933	263 (28.2)	5.7	94.2 vs 91.6	P = 0.01	-	Non SRC-GC
Kim et al[180], 2004	561	94 (16.8)	2.1	96.3 vs 90.8	NS	NS	Non SRC-GC
Kunisaki et al[185], 2004	513	120 (23.4)	9.2	Better	P = 0.033	P = 0.036	Non SRC-GC
Ha et al[186], 2008	1520	388 (25.5)	9.5	99.7 vs 99.1/97.2	NS/P = 0.019	-	WMD-PA/PD-MC
Zhang et al[45], 2010	138	49 (35.5)	-	Similar	NS	-	Non SRC-GC
Chiu et al[182], 2011	579	149 (25.7)	10.7	96.1 vs 89.6	P = 0.01	-	Non SRC-GC
Jiang et al[55], 2011	269	54 (20.1)	16.7	94.3 vs 90.6	P = 0.007	P = 0.011	Non SRC-GC
Kwon et al[50], 2014	326	51 (15.6)	9.8	84.0 vs 76.0/65.7 (10-yr survival rate)	NS	-	WD-MD/PD-MC
Kim et al[52], 2014	2085	345 (16.5)	9.0%	Similar (disease-related survival)	NS	-	WD/MD/PD
Wang et al[187], 2015	334	115 (34.4)	8.5	93.9 vs 85.8	P = 0.027	0.001	UD
Chon et al[53], 2017	3272	1091 (33.3)	-	95 vs 85 (10-yr survival rate)	P < 0.001	P = 0.041 (WMD)	WMD-PD
Imamura et al[188], 2016	746	152 (20.4)	2.0	97.4 vs 89.9	P = 0.012	P = 0.038	Non SRC-GC
Western studies
Gronnier et al[54], 2013	421	104 (24.7)	24,0	85 vs 76	P = 0.035	NS	Non SRC-GC
Bamboat et al[51], 2014	437	174 (39.8)	-	0 vs 8/24 (5-disease-specific mortality)	P = 0.001	-	WMD/PD

EGC: Early gastric cancer; LNM: Lymph node metastasis; SRC-GC: Signet ring cells-gastric cancer; non SRC-GC: Gastric cancer other types than SRC-GC; WMD: Well-and moderately-differentiated gastric cancer; PD: Poorly differentiated; MC: Mucinous cancer; NS: Non-significant.

Table 5 Summary of studies reporting prognostic value of signet ring cell- and poorly cohesive cell-gastric cancer

Studies	n	n SRC (%)	% LNM	5-yr survival rate % (PCC-GC vs other)	Univariate	Multivariate	Compared to
Eastern studies
Maehara et al[49], 1992	1116	23 (2.1)	60.8	42.5 vs 37.6	NS	-	Non SRC-GC
Kim et al[177], 1994	2917	265 (9.1)	80.8	33 vs 45.4/38.8/35.3	P < 0.05	-	WD/MD/PD
Otsuji et al[178], 1998	930	60 (6.4)	63.3	44.4 vs 27.5 (10-yr survival rate)	NS	-	Non SRC-GC
Yokota et al[179], 1998	430	52 (12.1)	-	Worse	NS	-	Non SRC-GC
Kunisaki et al[185], 2004	600	54 (9.0)	57.4	Similar	NS	-	Non SRC-GC
Kim et al[180], 2004	1797	110 (6.1)	47.3	35.1 vs 39.5	NS	-	Non SRC-GC
Li et al[56], 2007	4759	662 (13.9)	75.7	42.4 vs 50.1	0.009	NS	Non SRC-GC
Chiu et al[182], 2011	1860	356 (19.1)	71.6	41.5 vs 46.3	P = 0.018	-	Non SRC-GC
Jiang et al[55], 2011	2046	157 (7.7)	64.3	31.5 vs 35.7	NS	NS	Non SRC-GC
Zu et al[57], 2014	741	44 (5.9)	56.8	43.4 vs 87.1/57.1/50.6/62.7	P = 0.012	0.028	WD/MD/PD/MC
Kwon et al[50], 2014	443	57 (12.9)	73.7	26.0 vs 50.5/38.4 (10-yr survival rate)	P = 0.044	NS	WD-MD/PD-MC
Chon et al[53], 2017	1777	555 (31.2)	-	53 vs 58/52 (10-yr survival rate)	P < 0.001	P < 0.001	WMD/PD
Western studies
Heger et al[58], 2014	723	235 (32.5)	63.0	26.3 vs 46.6 mo (median survival)	P < 0.001	P = 0.02 (backward analysis)	Non SRC-GC

EGC: Early gastric cancer; LNM: Lymph node metastasis; SRC-GC: Signet ring cell-gastric cancer; PCC-GC: Poorly cohesive cells-gastric cancer; WMD: Well-and moderately-differentiated gastric cancer; PD: Poorly differentiated; MC: Mucinous cancer; NS: Non-significant.