Clinicopathological significance of histological diversity in gastric adenocarcinoma with primitive enterocyte phenotype: A methylation-driven aggressive entity

Table 1 The comparison of clinicopathologic features and stratification in gastric adenocarcinoma with primitive enterocyte phenotype

Parament	GAPEP (n = 134)	CGC-P (n = 92)	CGC (n = 274)	HAC (n = 49)	GAED (n = 63)	P value
						GAPEP vs CGC	GAPEP vs CGC-P	CGC-P vs CGC	HAC vs GAED
Age (years)						< 0.01	< 0.05	0.4103	< 0.05
> 65	74	38	100	21	39
≤ 65	60	54	174	28	24
Gender						0.407	0.4426	0.1206	0.568
Male	102	74	198	35	48
Female	32	18	76	14	15
Location						0.749	0.6455	0.4288	0.4778
Fundus-body and cardia	84	60	166	32	37
Antrum	51	32	108	17	26
Size (cm)						< 0.0001	< 0.0001	0.5841	0.2630
> 5	65	21	219	27	28
≤ 5	69	71	55	22	35
Histological grade						< 0.0001	< 0.01	0.4677	< 0.001
G1-2	92	47	128	25	53
G3	41	45	146	24	10
JGCA type						0.0001	0.0822	0.1309	< 0.001
Differentiated	99	58	148	26	54
Undifferentiated	35	34	126	23	9
Vascular invasion						0.846	0.6119	0.6883	0.1278
Positive	105	70	214	41	45
Negative	28	22	60	8	18
Perineural invasion						< 0.0001	< 0.05	0.1168	0.7850
Positive	98	58	158	37	46
Negative	31	34	136	12	17
T-staging						< 0.001	0.4323	< 0.0001	0.8249
T2-3	9	20	53	11	16
T4	124	72	221	38	47
AJCC-staging						0.6875	0.0967	0.127	0.5434
I-II	42	39	92	14	22
III-IV	91	53	182	35	41
Tumor budding						0.0656	0.6422	0.2247	NA
Bd1	16	16	47	NA	NA
Bd 2-3	43	52	227	NA	NA
MMR
pMMR	86	209	71	30	40	< 0.05	0.9554	0.0571	0.7564
dMMR	13	63	11	6	6
p53						0.001	0.5465	< 0.05	0.7880
Mutant type	81	59	128	28	42
Wild type	21	19	83	6	11
HER2						< 0.01	0.3301	0.1179	0.6284
Amplification	29	16	30	8	14
Not amplification	93	72	228	36	45

GAPEP: Gastric adenocarcinoma with primitive enterocyte phenotype; CGC: Conventional gastric cancer; CGC-P: Conventional gastric cancer expressing primitive phenotypic markers; HAC: Hepatoid adenocarcinoma; GAED: Gastric adenocarcinoma with enteroblastic differentiation; NA: Not available; JGCA: Japanese Gastric Cancer Association; AJCC: American Joint Committee on Cancer; MMR: Mismatched repair; pMMR: Proficient mismatched repair; dMMR: Defective mismatched repair; NA: Not available.

Table 2 The comparison of clinicopathologic features and stratification in gastric adenocarcinoma with primitive enterocyte phenotype

Parament	Statisticians	P value
		GAPEP (n = 31) vs CGC (n = 40)	GAPEP (n = 31) vs CGC-P (n = 157)	HAC (n = 12) vs GAED (n = 19)
Sex	χ2 test	0.652	0.893	0.518
Diagnosis age	Kruskal-Wallis test	< 0.05	0.0346	0.525
Lauren class	χ2 test	< 0.05	< 0.01	0.366
WHO class	χ2 test	< 0.05	< 0.05	0.216
TNM stage	χ2 test	0.572	0.129	0.435
AJCC stage	χ2 test	0.319	0.0878	0.778
T stage	χ2 test	0.071	-	-
NDS-AJCC	χ2 test	0.443	0.277	0.299
EBV present	χ2 test	0.48	0.132	0.814
Molecular-subtypes	χ2 test	< 0.0001	< 0.05	0.183
Fraction genome altered	Kruskal-Wallis test	< 0.0001	< 0.01	0.598
Copy number cluster	χ2 test	< 0.0001	< 0.05	0.295
Molecular subtype	χ2 test	< 0.001	< 0.05	0.136
Absolute extract ploidy	Kruskal-Wallis test	< 0.001	0.126	0.653
Methylation cluster	χ2 test	< 0.001	0.0688	0.0625
Gene expression cluster	χ2 test	< 0.05	< 0.05	< 0.05
CIMP category	χ2 test	< 0.05	0.167	< 0.05
Hyper-mutated	χ2 test	< 0.05	0.738	0.244
TP53 mutation	χ2 test	< 0.01	< 0.05	0.869
CDKN2A silencing	χ2 test	0.0622	0.26	0.0894
ARID1A mutation	χ2 test	< 0.05	0.175	0.249
MSI status	χ2 test	< 0.05	0.85	0.145
MLH1 silencing	χ2 test	0.0655	0.648	0.809
ERBB2 amplificated	χ2 test	< 0.05	0.2799	0.363
Percent tumor nuclei	Kruskal-Wallis test	0.285	< 0.05	0.0418
MET skipped exons 18 and 19	χ2 test	0.129	0.682	0.571
Percent lymphocyte infiltration	Kruskal-Wallis test	0.444	0.902	0.0833
ARHGAP26-ARHGAP6-CLDN18 rearrangement	χ2 test	0.86	0.821	0.814
KRAS mutation	χ2 test	0.156	0.123	-
PIK3CA mutation	χ2 test	0.15	0.42	0.613
MicroRNA expression cluster	χ2 test	0.377	0.0688	-
Mutation count	Kruskal-Wallis test	0.208	0.262	0.389
Mutation rate	Kruskal-Wallis test	0.19	0.285	0.378
MET skipped exon 2	χ2 test	0.957	0.105	0.237
TMB	Kruskal-Wallis test	0.18	0.378	0.655
RHOA mutation	χ2 test	0.239	-	-
Percent tumor cells	Kruskal-Wallis test	0.277	< 0.01	0.178
Estimated leukocyte percentage	Kruskal-Wallis test	< 0.05	0.101	0.372
Intestinal type subclass	χ2 test	0.133	0.257	0.527
Anatomic region	χ2 test	0.732	0.72	0.0754
NDS-AJCC	χ2 test	0.443	0.277	0.299
EBV present	χ2 test	0.48	0.132	0.814

GAPEP: Gastric adenocarcinoma with primitive enterocyte phenotype; CGC: Conventional gastric cancer; CGC-P: Conventional gastric cancer expressing primitive phenotypic markers; HAC: Hepatoid adenocarcinoma; GAED: Gastric adenocarcinoma with enteroblastic differentiation; WHO: World Health Organization; TNM: Tumor-node-metastasis staging; TMB: Tumor mutational burden; NDS, Nodal disease staging; AJCC: American Joint Committee on Cancer; EBV: Epstein-Barr virus; CIMP: CpG island methylator phenotype; MSI: Microsatellite stability; MET: Mesenchymal-epithelial transition factor gene.