Different types of tumor microvessels in stage I-IIIA squamous cell lung cancer and their clinical significance

Table 1 Baseline patient clinicopathological and treatment information

Clinical and pathological data	Patient groups				Significance level (P value)
	Main cohort (n = 180)		Training cohort (n = 62)
	n	%	n	%
Age (yr)
< 60	60	33.3	20	32.3	0.897
60-69	98	54.5	33	53.2
≥ 70	22	12.2	9	14.5
Tumor location
Central	119	66.1	38	61.3	0.493
Peripheral	61	33.9	24	38.7
Comorbidity
Absence	22	12.2	8	12.3	0.888
Presence	158	87.8	54	87.7
Histology
KSCC	56	31.1	21	33.9	0.687
NKSCC	124	68.9	41	66.1
Tumor grade
G1	57	31.7	23	37.1	0.325
G2	88	48.9	32	51.6
G3	35	19.4	7	11.3
T stage
T1a	9	5.0	8	12.9	0.039a
T1b	15	8.3	6	9.7
T2a	82	45.6	34	54.8
T2b	17	9.4	5	8.1
T3	57	31.7	9	14.5
N stage
N0	48	26.7	22	35.5	0.411
N1	88	48.9	26	41.9
N2	44	24.4	14	22.6
Stage
I	30	16.7	20	32.3	0.03a
II	73	40.6	22	32.4
III	77	42.8	20	32.3
Type of surgery
Lobectomy	84	46.7	40	64.4	0.001a
Bilobectomy	6	3.3	5	8.1
Pneumonectomy	86	47.8	13	21.0
Segmentectomy	4	2.2	4	6.5
Adjuvant therapy
Absent	51	28.3	27	43.5	0.002a
Chemotherapy	68	37.8	10	16.1
Radiation therapy	38	21.1	21	33.9
Chemo- and radiotherapy	23	12.8	4	6.5

^aP < 0.05, the differences between groups are statistically significant.

KSCC: Keratinizing squamous cell carcinoma; NKSCC: Nonkeratinizing squamous cell carcinoma.

Table 2 Correlations between different types of tumor microvessels and characteristics of the parenchymal and stromal components of lung squamous cell carcinoma

	Fragmentation in the tumor solid component		The presence of LFFCT in the tumor stroma		Retraction clefts		Tumor spread in the AASs
	Gamma	P value	Gamma	P value	Gamma	P value	Gamma	P value
MVD	0.240	0.24	0.034	0.84	0.042	0.79	-0.537	0.002a
DCs	0.064	0.66	0.014	0.90	0.211	0.06	-0.251	0.04a
ADCs	0.555	0.0006a	-0.537	0.0005a	0.115	0.45	0.248	0.15
SPELs	0.071	0.65	0.124	0.43	0.517	0.0006a	0.435	0.007a
DCs with weak expression of CD34	0.297	0.14	0.943	0.0000a	0.193	0.21	-0.210	0.22
Contact-type DCs	0.344	0.03a	0.502	0.001a	0.666	0.0000a	-0.077	0.66
The capillaries in the tumor solid component	0.040	0.82	0.009	0.96	0.231	0.16	-0.069	0.72
LVs in lymphoid and polymorphic cell infiltrates	-0.538	0.001a	0.054	0.75	0.284	0.07	0.302	0.08

^aP < 0.05, the differences between groups are statistically significant.

AASs: Alveolar air spaces; ADCs: Atypical dilated capillaries; DCs: Dilated capillaries; LFFCT: Loose, fine fibrous connective tissue in the tumor stroma; LVs: Lymphatic vessels; MVD: Microvessel density; SPELs: Structures with partial endothelial lining; CD34: Cluster of differentiation 34.

Table 3 Univariate and multifactorial logistic regression analysis of risk factors for regional lymph node metastases in patients with lung squamous cell carcinoma

Characteristic	Univariate analysis, OR (95%CI)	P value	Multivariate analysis, OR (95%CI)	P value
Age
< 60	1	-
60-69	1.48 (0.71-3.07)	0.291
≥ 70	0.75 (0.27-2.10)	0.584
Tumor location
Peripheral	1	-	1	-
Central	4.77 (2.36-9.63)	0.0000a	7.80 (3.33-18.26)	0.0000a
Histology
KSCC	1	-
NKSCC	0.77 (0.37-1.60)	0.482
Tumor grade
G1	1	-
G2	1.07 (0.50-2.29)	0.858
G3	0.78 (0.31-1.97)	0.597
T stage
T1a	1	-	1	-
T1b	5.50 (0.91-33.18)	0.063	4.93 (0.76-31.78)	0.093
T2a	6.20 (1.42-27.09)	0.015a	2.82 (0.59-13.53)	0.195
T2b	9.33 (1.45-60.21)	0.019a	5.27 (0.75-37.28)	0.096
T3	5.60 (1.24-25.25)	0.026a	1.66 (0.31-8.80)	0.551
DCs with weak expression of CD34
Absence	1	-
Presence	1.10 (0.56-2.15)	0.783
DCs of "contact type"
Presence	1	-
Absence	1.67 (0.86-3.25)	0.13
The capillaries in the tumor solid component
Absence	1	-	1	-
Presence	2.89 (1.33-6.28)	0.008a	2.72 (1.14-6.48)	0.023a
LFFCT in the tumor stroma
Absence	1	-
Presence	0.70 (0.32-1.55)	0.383
Fragmentation in the tumor solid component
Absence	1	-	1	-
Presence	2.55 (1.28-5.06)	0.008a	3.03 (1.33-6.94)	0.009a
Retraction clefts
Absence	1	-	1	-
Presence	2.62 (1.33-5.16)	0.005a	3.52 (1.56-7.96)	0.003a
Tumor spread through the AAS
Absence	1	-
Presence	0.72 (0.37-1.42)	0.342

^aP < 0.05, the differences between groups are statistically significant.

AASs: Alveolar air spaces; DCs: Dilated capillaries; KSCC: Keratinizing squamous cell carcinoma; LFFCT: Loose, fine fibrous connective tissue in the tumor stroma; NKSCC: Nonkeratinizing squamous cell carcinoma; OR: Odds ratio.

Table 4 Univariate and multivariate analyses for the predictors of disease recurrence in patients with lung squamous cell carcinoma

Characteristic	Univariate analysis, OR (95%CI)	P value	Multivariate analysis, OR (95%CI)	P value
Age
< 60	1	-
60-69	1.87 (0.97-3.58)	0.06
≥ 70	2.45 (0.89-6.72)	0.082
Tumor location
Peripheral	1	-	1	-
Central	1.86 (0.99-3.47)	0.052a	1.04	0.92
Histology
KSCC	1	-
NKSCC	1.79 (0.94-3.38)	0.075
Tumor grade
G1	1	-	1	-
G2	1.51 (0.76-2.95)	0.232	1.36 (0.59-3.01)	0.466
G3	3.44 (1.39-8.48)	0.007a	4.24 (1.37-13.14)	0.001a
T stage
T1a	1	-
T1b	7.00 (1.04-46.95)	0.045a
T2a	4.26 (0.83-21.74)	0.082
T2b	5.00 (0.79-31.62)	0.087
T3	3.38 (0.65-17.69)	0.149
N stage
N0	1	-	1	-
N1	2.00 (0.97-4.11)	0.059	1.89 (0.81-4.39)	0.137
N2	3.22 (1.37-7.57)	0.007a	3.43 (1.26-9.34)	0.016a
Stage
I	1	-	1	-
II	2.17 (0.89-5.27)	0.088	1.87 (0.45-7.69)	0.385
III	3.13 (1.29-7.60)	0.012a	3.44 (0.50-23.49)	0.207
Adjuvant therapy
Radiation therapy	1	-	1	-
Chemo- and radiotherapy	1.41 (0.50-3.97)	0.513	0.57 (0.16-1.98)	0.376
Chemotherapy	3.02	0.008	2.07 (0.78-5.53)	0.146
DCs with weak expression of CD34
Absence	1	-	1	-
Presence	4.26 (2.25-8.05)	0.0000a	1.18 (0.43-3.23)	0.749
Contact-type DCs
Absence	1	-
Presence	0.97 (0.54-1.75)	0.934
The capillaries in the tumor solid component
Absence	1	-	1	-
Presence	2.32 (1.24-4.35)	0.008a	1.20 (0.56-2.59)	0.638
LFFCT in the tumor stroma
Absence	1	-	1	-
Presence	6.24 (2.85-13.67)	0.0000a	7.34 (3.03-17.76)	0.0000a
Fragmentation of the tumor solid component
Absence	1	-	1	-
Presence	3.03 (1.58-5.82)	0.0009a	5.23 (2.27-12.07)	0.0001a
Retraction clefts
Absence	1	-
Presence	0.71 (0.38-1.29)	0.262
Tumor spread through the AASs
Presence	1	-	1	-
Absence	2.06 (1.13-3.76)	0.019a	3.37 (1.22-5.66)	0.0083a

^aP < 0.05, the differences between groups are statistically significant.

AASs: Alveolar air spaces; DCs: Dilated capillaries; KSCC: Keratinizing squamous cell carcinoma; LFFCT: Loose, fine fibrous connective tissue in the tumor stroma; NKSCC: Nonkeratinizing squamous cell carcinoma; OR: Odds ratio; CD34: Cluster of differentiation 34.