Histotype-based prognostic classification of gastric cancer

Table 1 Survival analysis of 200 gastric cancers (Varese series) according to tumor node metastasis stage

				Cox survival analysis
Stage	n (%)	Death rate	95% CI	HR	95% CI	P value
I	40 (20)	1.63	0.81-3.25	1
II	61 (30.5)	13.67	10.06-18.56	5.64	2.63-12.09	< 0.001a
III	68 (34)	26.04	19.74-34.46	9.49	4.45-20.24	< 0.001b
IV	31 (15.5)	52.66	36.11-76.79	18.90	8.41-42.46	< 0.001c

^aP = 0.001 vs III + IV;

^bP = 0.015 vs II ;

^cP = 0.004 vs III. CI: Confidence intervals; HR: Hazard ratio.

Table 2 Survival analysis of 200 gastric cancers according to histotype-based grade and according to Lauren classification

				Cox survival analysis
						P value
	n (%)	Death rate	95% CI	HR	95% CI	Univariate	With stage
Grade
1	44 (22)	3.35	2.02-5.55	1
2	142 (71)	17.24	14.16-21.90	3.5	2.02-6.05	< 0.001	0.004
3	14 (7)	95.66	54.33-168.45	9.64	4.41-21.06	< 0.001a	< 0.001b
Lauren type1
Intestinal	116 (58)	8.86	6.93-11.31	1
Diffuse	50 (25)	21.08	15.20-29.22	1.71	1.13-2.57	0.011	0.362
Unclassified	34 (17)	18.4	12.53-27.03	1.7	1.07-2.68	0.023	0.165

^aP = 0.001 vs grade 2;

^bP = 0.019 vs grade 2. Harrell’s c = 0.63.

¹F: Univariate model: χ² (2γ) = 8.67, P = 0.013. Harrell's c = 0.57. Stage-inclusive model: P = 0.341 for Lauren classification. CI: Confidence intervals; HR: Hazard ratio.

Table 3 Survival analysis of 492 tumors (Varese + Pavia series) according to histotype and grade

					Cox survival analysis
	n (%)						P value
	Varese series	Joint series	Death rate	95% CI	HR1	95% CI	Univariate	With stage
Grade 1	44 (22)	132 (26.8)	2.54	1.80-3.57	1
HLR	38 (19)	82 (16.6)	3.67	2.50-5.39	1
WD tubular	2 (1)	13 (2.6)	0
Lg diff.desm	2 (1)	17 (3.5)	1.50	0.48-4.64	0.43	0.13-1.42	0.167	0.109
muconodular	2 (1)	20 (4.1)	1.67	0.63-4.44	0.51	0.18-1.46	0.211	0.271
Grade 2	142 (71)	307 (62.4)	15.97	13.96-18.28	4.91	3.40-7.11	< 0.001	< 0.001
Mucinous ord.	4 (2)	10 (2.0)	11.50	5.16-25.59	2.16	0.89-5.24	0.090a	0.987b
Cohesive ord.	95 (47.5)	196 (39.8)	15.28	12.89-18.11	3.43	2.25-5.23	< 0.001	0.001
Diffuse ord.	43 (21.5)	101 (20.6)	18.09	14.36-22.79	3.96	2.53-6.22	< 0.001	< 0.001
Grade 3	14 (7)	53 (10.8)	108.84	82.02-144.43	18.47	11.56-29.50	< 0.001c	< 0.001c
Mucinous Hg.	3 (1.5)	21 (4.3)	100.0	64.07-160.0	11.54	6.32-21.48	< 0.001	< 0.001
Anaplastic	11 (5.5)	32 (6.5)	120.0	80.01-170.0	14.11	8.17-24.39	< 0.001	< 0.001

¹For grades, based on grade 1; for histotypes, based on high lymphoid response (HLR) type.

^aP = 0.005 vs muconodular and P < 0.001 vs mucinous.

^bP = 0.037 vs muconodular and P < 0.001 vs mucinous.

^cP < 0.001 vs grade 2. Harrell’s c = 0.69 for the 3 grades and 0.71 for the 9 histotypes. CI: Confidence intervals; HR: Hazard ratio; WD: Well differentiated; diff.desm: Diffuse desmoplastic; ord.: Ordinary; Hg.: High-grade.

Table 4 Three subtypes of high lymphoid response tumors and comparison with non-high lymphoid response high-level microsatellite DNA instability cases (Pavia and Varese series)

				Cox survival analysis
						P value
	n (%)	Death rate	95% CI	HR	95% CI	Univariate	With stage
HLR+
EBV+	24 (29.6)1	7.38	4.09-13.33	2.39	1.03-5.53	0.042	0.817
MSI-H	40 (49.4)	3.01	1.67-5.44	1
EBV-/MSI-	17 (21.0)	2.27	0.85-6.06	0.81	0.26-2.53	0.711	0.393
HLR-
MSI-H	38 (48.7)2	12.29	8.24-18.33	3.64	1.78-7.47	< 0.001	0.015

¹One EBV⁺/MSI^- case omitted;

²% of all MSI-H cases, HLR⁺ or

^-. HLR: High lymphoid response; EBV: Epstein-Barr virus; MSI-H: High-level microsatellite DNA instability.