Clinicopathological features and prognostic factors associated with gastroenteropancreatic mixed neuroendocrine non-neuroendocrine neoplasms in Chinese patients

Table 1 Patients’ characteristics

Variable	Frequency (n)	Ratio (%)
Gender
Male	34	73.9
Female	12	26.1
Age (yr)	66 (41-84)
< 65	20	43.5
≥ 65	26	56.5
Location
Stomach	35	76.1
Intestine	9	19.6
Pancreas	2	4.3
Size (cm)	5.4 (0.5-18)
< 5 cm	25	54.3
≥ 5 cm	21	45.7
Ki- 67 index
< 50%	17	37.0
≥ 50%	29	63.0
Proportions of two components
NEC higher	28	60.9
AC higher	18	39.1
Histological grade of adenocarcinoma
Moderately differentiated	13	28.3
Poorly differentiated	33	71.7
Neuroendocrine component
NET	0	0
NEC	46	100
Lymph node metastasis
Presence	34	73.9
Absence	12	26.1
Vascular tumor thrombus
Presence	26	56.5
Absence	20	43.5
Neurological recidivism
Presence	27	58.7
Absence	19	41.3
Distant metastasis
Presence	14	30.4
Absence	32	69.6
Clinical TNM stage
I + II	13	28.3
III	23	50.0
IV	10	21.7

NET: Neuroendocrine tumors; NEC: Neuroendocrine carcinomas.

Table 2 Univariate analysis of overall survival

Variable	n	Log-rank	P value
Gender		0.537	0.464
Male	31
Female	11
Age (yr)		4.815	0.028
< 65	17
≥ 65	25
Location		5.747	0.056
Stomach; Intestine	32; 8
Pancreas	2
Size (cm)		5.106	0.024
< 5 cm	22
≥ 5 cm	20
Ki-67 index		9.349	0.002
< 50%	17
≥ 50%	25
Proportion of the two components		9.421	0.002
NEC higher	26
AC higher	16
Histological grade of adenocarcinoma		11.303	0.001
Moderately differentiated	13
Poorly differentiated	29
Lymph node metastasis		8.800	0.003
Presence	32
Absence	10
Vascular tumor thrombus		12.250	< 0.001
Presence	25
Absence	17
Neurological recidivism		11.056	0.001
Presence	26
Absence	16
Distant metastasis		44.917	< 0.001
Presence	10
Absence	32
Clinical TNM stage		48.942	< 0.001
I + II	13
III	19
IV	10

NEC: Neuroendocrine carcinomas; TNM: Tumor node metastasis.

Table 3 Multivariate Cox regression analysis results of overall survival

Variable	B	SE	Wald χ2	P value	HR	95%CI
Ki-67 index	1.452	0.546	7.078	0.008	4.273	1.466-12.459
Lymph node metastasis	1.869	0.693	7.277	0.007	6.481	1.667-25.197
Distant metastasis	-1.962	0.686	8.171	0.004	0.141	0.037-0.540
NEC/AC proportion	1.243	0.602	4.262	0.039	3.467	1.065-11.286
Clinical stage	-1.374	0.610	5.070	0.024	0.253	0.077-0.837

NEC: Neuroendocrine carcinomas; CI: Confidence interval; HR: Hazard ratio.

Table 4 Comparative of mixed neuroendocrine-non-neuroendocrine neoplasms, neuroendocrine tumors, and neuroendocrine carcinomas

Variable	NET (n = 55)	NEC (n = 47)	MiNEN (n = 46)	P value
				NET vs MiNEN	NEC vs MiNEN
Male/female	24/31	34/13	34/12	0.004	0.864
Age [yr, mean (range)]	49 (11-85)	64 (40-83)	65 (41-84)	< 0.001	0.857
Location				< 0.001	0.162
Stomach	7	26	35
Intestine	39	15	9
Pancreas	9	6	2
Size [cm, mean (range)]	1.7 (0.2-11)	5.2 (1.5-16.0)	5.4 (0.5-18)	< 0.001	0.742
Ki-67 index				< 0.001	0.051
< 2%	15	2	0
2%-20%	39	5	1
> 20%	1	40	45
Lymph node				< 0.001	0.691
metastasis
Presence	13	33	34
Absence	42	14	12
Distant metastasis				< 0.001	0.156
Presence	2	21	14
Absence	53	26	32
Survival time				< 0.001	0.001
(mo)
Median	50	14	30
Mean	49.3	34	28.6
Follow-up				< 0.001	0.054
Dead	3	34	27
Alive	44	7	15

MiNEN: Mixed neuroendocrine-non-neuroendocrine neoplasms; NET: Neuroendocrine tumors; NEC: Neuroendocrine carcinomas.

Table 5 Comparison between patients with mixed neuroendocrine-non-neuroendocrine neoplasms and those with poorly differentiated adenocarcinoma

Variable	Poorly differentiated adenocarcinoma (n = 58)	MiNEN (n = 46)	P value
Male/female	37/21	34/12	0.271
Mean age, years, (range)	61 (31-81)	65 (41-84)	0.055
Location			0.836
Stomach	42	35
Intestine	12	9
Pancreas	4	2
Size (cm)			0.254
< 5	25	25
≥ 5	33	21
Ki- 67 index			0.104
< 50%	13	17
≥ 50%	45	29
Lymph node metastasis			0.385
Presence	47	34
Absence	11	12
Distant metastasis			0.750
Presence	16	14
Absence	42	32
Clinical TNM stage			0.402
I + II	10	13
III	34	23
IV	14	10
Survival time (mo)			0.453
Median	18	30
Mean	24.3	28.6
Follow-up			0.863
Dead	33	27
Alive	17	15

MiNEN: Mixed neuroendocrine-non-neuroendocrine neoplasms; TNM: Tumor node metastasis.