Background
Methods
Patients
Gastric carcinoma cases
Non-neoplastic gastric tissue
Pathological evaluation
Immunohistochemistry
Assessment of immunohistochemical stain of iNOS
Assessment of immunohistochemical stain of D2-40: Lymphatic invasion (LI), lymphatic invasion density (LID [nLI/mm2]), and lymphatic vascular density (LVD)
Statistical analysis
Results
Clinical and pathological findings
Clinicopathologic variables | Number of cases (n) | Percent (%) |
---|---|---|
Age (years) | 62.00 ± 10.94 (range: 35–82) | |
Tumor size (cm) | 6.46 ± 2.66 (range: 2–13) | |
Gender | ||
Male | 26 | 63.4 |
Female | 15 | 36.6 |
Location of tumor | ||
Cardia | 13 | 31.7 |
Corpus | 6 | 14.6 |
Antrum | 22 | 53.7 |
Borrmann type | ||
I | 0 | 0 |
II | 6 | 14.6 |
III | 26 | 63.4 |
IV | 9 | 22 |
Lauren classificafion | ||
Intestinal | 19 | 46.3 |
Diffuse | 7 | 17.1 |
Mixed | 15 | 36.6 |
Histological type | ||
NOS/tubular/papillary | 31 | 75.6 |
Mucinous/poorly cohesive | 10 | 24.4 |
Differentiation | ||
Well/moderate | 20 | 48.7 |
Poorly/signet ring cell | 21 | 51.3 |
Nodal status | ||
pN0 | 9 | 22 |
pN1 | 7 | 17.1 |
pN2 | 12 | 29.2 |
pN3 | 13 | 31.7 |
Depth of invasion | ||
pT1 | 2 | 4.9 |
pT2 | 2 | 4.9 |
pT3 | 25 | 61 |
pT4 | 12 | 29.2 |
Stage (TNM) | ||
I | 3 | 7.3 |
II | 16 | 39.1 |
III | 22 | 53.6 |
IV | 0 | 0 |
Inflammatory response | ||
Score 0 | 0 | 0 |
Score 1 | 11 | 26.8 |
Score 2 | 12 | 29.3 |
Score 3 | 18 | 43.9 |
Lymphovascular invasion [H&E] | ||
Positive | 31 | 75.6 |
Negative | 10 | 24.4 |
Lymphatic invasion [D2-40] | ||
Positive | 35 | 85.4 |
Negative | 6 | 14.6 |
Immunohistochemical findings
iNOS
Gastric carcinoma cases
Variables | iNOS Score [Mean ± SD (Min.-Max.)] | ||
---|---|---|---|
iNOS-T | iNOS-F | iNOS-E | |
Histological type
| |||
NOS/tubular/papillary | 2.6 ± 2.3 (0–6) | 4.8 ± 1.7 (2–8) | 5.9 ± 2.1 (2–8) |
Mucinous/poorly cohesive | 4.8 ± 2.2 (2–8) | 4.4 ± 1.9 (2–7) | 5.9 ± 2.7 (2–8) |
Differentiation
| |||
Well/moderate | 2.6 ± 2.3 (0–6) | 4.6 ± 2.2 (0–8) | 5.6 ± 2.8 (2–8) |
Poorly/signet ring cell | 4.8 ± 2.2 (2–8) | 4.3 ± 1.3 (0–8) | 6.0 ± 1.6 (2–8) |
pN
| |||
N0
| 1.3 ± 1.8 (0–5) | 2.9 ± 1.3 (2–5) | 3.2 ± 1.9 (2–7) |
N1 | 4.1 ± 1.3 (2–6) | 5.9 ± 1.6 (4–8) | 6.7 ± 1.7 (4–8) |
N2 | 4.1 ± 1.9 (2–8) | 4.9 ± 1.2 (3–7) | 6.6 ± 1.3 (4–8) |
N3 | 5.9 ± 2.2 (2–8) | 5.2 ± 1.2 (3–7) | 6.6 ± 1.1 (4–8) |
pT
| |||
T1 | 1.5 ± 1.1 (0–7) | 2.4 ± 1.2 (2–7) | 3.1 ± 1.7 (2–7) |
T2 | 4.2 ± 1.5 (2–6) | 5.4 ± 1.7 (4–8) | 6.8 ± 1.8 (4–8) |
T3 | 4.4 ± 1.9 (2–8) | 4.9 ± 1.5 (3–7) | 6.2 ± 1.7 (4–8) |
T4 | 5.9 ± 2.1 (2–8) | 5.1 ± 1.4 (3–7) | 6.9 ± 1.2 (4–8) |
TNM stage
| |||
I | 0.0 ± 0.0 (0–0) | 3.3 ± 1.5 (2–5) | 4.0 ± 2.6 (2–7) |
II | 3.2 ± 1.8 (0–6) | 4.4 ± 1.9 (2–8) | 5.0 ± 2.4 (2–8) |
III | 5.4 ± 3.2 (2–8) | 5.3 ± 1.3 (3–7) | 6.8 ± 1.0 (4–8) |
IV | - | - | - |
Total
| 4.0 ± 2.5 (0–8) | 4.0 ± 2.5 (0–8) | 5.9 ± 2.0 (2–8) |
Non-neoplastic gastric tissue
D2-40
Lymphatic invasion density (LID [nLI/mm2])
Intratumoral (I-LVD) and peritumoral lymphatic vascular density (P-LVD)
Variables | Mean ± SD (Min.-Max.) | ||
---|---|---|---|
LID | P-LVD | I-LVD | |
Histological type
| |||
NOS/tubular/papillary | 0.06 ± 0.16 (0–0.8) | 12.8 ± 2.7 (7.2–15.7) | 6.9 ± 4.4 (1–24.3) |
Mucinous/poorly cohesive | 0.11 ± 0.13 (0–0.8) | 13.8 ± 5.4 (5.9–21.6) | 6.9 ± 2.6 (3.5–10) |
Differentiation
| |||
Well/moderate | 0.01 ± 0.01 (0–0.03) | 10.2 ± 2.7 (7.2–15.7) | 5.2 ± 2.1 (1–8.7) |
Poorly/signet ring cell | 0.10 ± 0.18 (0–0.88) | 14.5 ± 6.2 (5.7–32) | 6.9 ± 2.6 (3.5–10.2) |
pN
| |||
N0
| 0.001 ± 0.003 (0–0.03) | 8.1 ± 1.7 (5.9–11.7) | 3.5 ± 1.5 (1–5.5) |
N1 | 0.02 ± 0.01 (0–0.04) | 8.6 ± 1.9 (5.7–11) | 4.8 ± 1.9 (3–8.7) |
N2 | 0.03 ± 0.03 (0–0.02) | 12..6 ± 2.5 (9–17.5) | 6.8 ± 1.9 (3.5–9.3) |
N3 | 0.18 ± 0.2(0–0.9) | 19.1 ± 5.3 (13.7–32) | 10.6 ± 4.4 (6–24.3) |
pT
| 0.001 ± 0.003 (0–0.03) | 8.1 ± 1.7 (5.9–11.7) | 3.5 ± 1.5 (1–5.5) |
T1 | 0.0 ± 0.0 (0–0) | 7.9 ± 1.1 (7.2–8.7) | 3.9 ± 0.6 (3.4–4.3) |
T2 | 0.0 ± 0.01 (0–0.01) | 10.8 ± 7.2 (5.7–16) | 6.4 ± 3.2 (4.1–8.7) |
T3 | 0.04 ± 0.05 (0–0.27) | 11.8 ± 4.1 (5.9–22.1) | 5.9 ± 2.8 (1–11.3) |
T4 | 0.16 ± 0.3 (0–0.88) | 19.1 ± 5.3 (13.7–32) | 9.6 ± 5.2 (4.3–24.3) |
TNM stage
| |||
I | 0.0 ± 0.0 (0–0) | 7.7 ± 0.9 (7.2–8.7) | 2.9 ± 1.7 (1–4.3) |
II | 0.01 ± 0.02 (0.0–0.05) | 9.5 ± 2.9 (5.7–16) | 4.6 ± 1.9 (1.1–8.7) |
III | 0.13 ± 0.2 (0.01–0.88) | 16.2 ± 5.6 (9–32) | 9 ± 4.2 (7.9–11.5) |
IV | - | - | - |
Total
| 0.07 ± 0.15 (0–0.88) | 13.1 ± 5.7 (5.7–32) | 6.9 ± 3.9 (1–24.3) |
Non-neoplastic gastric mucosa
Statistical analysis
iNOS activity in tumor tissue specimens: correlation with clinicopathological parameters and lymphangiogenesis
iNOS expression in tumor cells (iNOS-T)
iNOS expression in tumor-associated stromal fibroblasts (iNOS-F)
iNOS activity in endothelial cells (iNOS-E)
D2-40
LID (nLI/mm2) and LVD: correlation with clinicopathologic parameters
LID (nLI/mm2)
I-LVD and P-LVD
Variables | iNOS score | D2-40 | ||||
---|---|---|---|---|---|---|
iNOS-T | iNOS-S | iNOS-E | LID | P-LVD | I-LVD | |
Age*
| ||||||
r value | 0.007 | 0.008 | 0.07 | 0.06 | 0.05 | 0.01 |
p Value | 0.92 | 0.96 | 0.86 | 0.71 | 0.99 | 0.85 |
Gender ( male or female)** | ||||||
p Value | 0.67 | 0.93 | 0.34 | 0.84 | 0.20 | 0.15 |
Location of tumor (proximal or distal) ** | ||||||
p Value | 0.53 | 0.17 | 0.005 | 0.95 | 0.77 | 0.60 |
Tumor size (cm)*
| ||||||
r value | 0.31 | 0.06 | 0.06 | 0.29 | 0.53 | 0.37 |
p Value | 0.05 | 0.70 | 0.70 | 0.07 | < 0.001 | 0.01 |
Histological type ( NOS/tubular/papillary or mucinous/poorly cohesive) ** | ||||||
p Value | 0.46 | 0.54 | 0.51 | 0.14 | 0.44 | 0.62 |
Differentiation ( Well/moderate or poorly/signet ring cell) ** | ||||||
p Value | 0.01 | 0.748 | 0.92 | 0.001 | 0.001 | 0.03 |
Inflammatory response (score 1 + 2 or score 3) ** | ||||||
p value | 0.01 | 0.89 | 0.51 | 0.02 | 0.001 | 0.01 |
LVI [H& E](positive or negative) ** | ||||||
p Value | 0.002 | 0.03 | 0.01 | 0.001 | 0.001 | < 0.001 |
LI [D2-40](positive or negative) ** | ||||||
p Value | 0.002 | 0.02 | 0.01 | < 0.001 | 0.001 | < 0.001 |
nLI*
| ||||||
r value | 0.64 | 0.37 | 0.44 | 0.98 | 0.65 | 0.63 |
p Value | < 0.001 | 0.017 | 0.004 | < 0.001 | < 0.001 | < 0.001 |
nNm*
| ||||||
r value | 0.61 | 0.30 | 0.40 | 0.83 | 0.86 | 0.78 |
p Value | < 0.001 | 0.05 | 0.009 | < 0.001 | < 0.001 | < 0.001 |
pN (N0 or N1/2/3) ** | ||||||
p Value | 0.001 | 0.003 | 0.023 | < 0.001 | < 0.001 | < 0.001 |
pT (T1 + 2 orT3 + 4) ** | ||||||
p Value | 0.05 | 0.70 | 0.70 | 0.07 | < 0.001 | 0.01 |
TNM stage (I + II or III + IV) ** | ||||||
p Value | 0.0002 | 0.067 | 0.02 | < 0.001 | < 0.001 | < 0.001 |
Variables | iNOS-T | iNOS-F | iNOS-E | LID | P-LVD | I-LVD |
---|---|---|---|---|---|---|
LID
| ||||||
r value
| 0.64 | 0.39 | 0.45 | - | 0.65 | 0.63 |
p value
| 0.001 | 0.013 | 0.004 | - | 0.001 | 0.001 |
P-LVD
| ||||||
r value
| 0.56 | 0.27 | 0.35 | 0.65 | - | 0.84 |
p value
| 0.001 | 0.08 | 0.02 | 0.001 | - | 0.001 |
I-LVD
| ||||||
r value
| 0.59 | 0.32 | 0.25 | 0.63 | 0.84 | - |
p value
| 0.001 | 0.04 | 0.11 | 0.001 | 0.001 | - |