Objective To investigate the clinical meanings of lymphangiogenesis, lymph vessel invasion (LVI) and lymph node (LN) micrometastasis in gastric cancer. Methods The expression of D2-40 in 68 patients with gastric cancer of primary lesion and the expressions of CK20 and (or) CKpan in 791 lymph nodes from 51 cases which were detected by immunohistochemical staining were analyzed, as well as their clinicopathologic profiles. The relationship of lymph vessel density (LVD), LVI and LN micrometastasis with LN metastasis and other clinicopathologic parameters was analyzed respectively. Results Positive rate of LVI with HE (LVI-HE) and D2-40 (LVI-IM) staining was respectively 66.2%(45/68) and 76.5%(52/68), P=0.118. The positive rate of LVI-IM was related to deeper tumor invasion (P=0.044), later stage of TNM (P=0.003) and LN metastasis (P=0.000). Average LVD of 68 cases was (18.19±7.44)/HP. The increment of LVD was significantly associated with LVI-HE positive status （P=0.040）, LVI-IM positive status （P=0.001）, venous invasion （P=0.037）, later stage of TNM （P=0.020） and LN metastasis （P=0.001）. The survival rate of the group sharing ≥15/HP of LVD was significantly lower than that in the group sharing ≤14/HP of LVD in early period of follow-up （P=0.032）. The incidence of nodal involvement in 51 patients was increased from 74.5%(38/51) by HE staining to 88.2%(45/51) by CK (CK20 or CKpan) immunostaining. The detection rate of metastasized LN was increased from 32.0%（253/791） by HE staining to 41.5%（328/791） by CK immunostaining (Plt;0.001). The significant difference of LN micrometastasis detection rate between CK20 (8.7%) and CKpan (12.3%) was also identified (P=0.003). The increased number of LN micrometastasis was related to larger diameter of tumor (P=0.001), higher LVI-HE positive rate (P=0.040), deeper invasion of tumor (P=0.018) and later stage of TNM (P=0.012). Both LN stage and TNM stage were changed according to the detection of LN micrometastasis: Seven patients of N0 should be recognized as N1 (N0→N1)， 6 as N1→N2, 1 as N2→N3. Four patients of stage Ⅰb should be recognized as stage Ⅱ (Ⅰb→Ⅱ)， 4 as Ⅱ→Ⅲa， 3 as Ⅲa→Ⅲb， 1 as Ⅲb→Ⅳ. Conclusion Detection of D2-40 and CK in diagnosis of LVI and LN micrometastasis is better than HE staining. The combined detection of CK20 and CKpan may be much easier to find out the LN with micrometastasis. Later stage of TNM the tumor is, more frequently the LN micrometastasis happens. The relationships of LVI-IM, LVD and LN micrometastasis with LN metastasis in gastric cancer has been demonstrated. Patients with higher LVD share a lower survival rate in early period of follow-up.
ObjectiveTo investigate the expressions of contactin-1 (CNTN-1), vascular endothelial growth factor-C (VEGF-C), and its receptor VEGFR-3 (Flt-4) in primary gastric cancer and to explore the relevance among them and their correlation with clinicopathologic features of gastric cancer. MethodsThe VEGF-C, VEGFR-3, and CNTN-1 protein expressions of tumor tissues and normal gastric mucosa tissues in 68 patients with primary gastric cancer were analyzed by immunohistochemistry. The Flt-4-positive vessel density (FVD) and lymphatic vessel density (LVD) were also analyzed by VEGFR-3positive and D2-40-positive staining, respectively. ResultsThe positivity rate of VEGF-C, VEGFR-3, and CNTN-1 protein expression in the primary tumor was 57.4% (39/68), 60.3% (41/68), and 55.9% (38/68), respectively, which was significantly higher than that in the normal gastric mucosa tissues 〔20.6% (14/68), 23.5% (16/68), and 16.2% (11/68)〕， P=0.000. The expressions of VEGF-C, VEGFR-3, and CNTN-1 protein were significantly correlated with TNM stage, lymphatic vessel invasion, and lymph node metastasis (Plt;0.05). The expression of CNTN-1 protein was significantly correlated with VEGF-C (r=0.372, P=0.002) and VEGFR-3 protein expression (r=0.308, P=0.011). In tumor tissues of sixtyeight patients the FVD was (10.41±9.38)/HP, which was significantly lower than LVD 〔(18.19±7.44)/HP〕, P=0.000. Elevated FVD and LVD was significantly found in patients with tumor characterized by later TNM stage, severer lymphatic vessel invasion, and severer lymph node metastasis (Plt;0.05). The FVD of tumor was significantly correlated with VEGF-C (P=0.029) and CNTN-1 protein expression (P=0.003). The LVD of tumor was not significantly correlated with CNTN-1 (P=0.727), VEGF-C (P=0.173), and VEGFR-3 protein expression (P=0.924). The patients with positive expression of VEGF-C, VEGFR-3, and CNTN-1 protein showed poorer prognosis (Plt;0.05). ConclusionsElevated expression of CNTN-1 protein is observed in primary gastric cancer and correlated with VEGF-C and VEGFR-3 protein expression, indicating that combined detection has great value in prediction of invasive potential and prognosis. VEGF-C-mediated CNTN-1 overexpression may promote lymphatic invasion via lymphangiogenesis pathway in patients with gastric cancer.
Objective To study the expression and significance of CCR chemokine receptor-7 (CCR7) protein and vascular endothelial growth factor-D (VEGF-D) protein in the progression of breast cancer, including normal breast tissue, slight and moderate atypical hyperplasia, severe atypical hyperplasia and intraductal carcinoma in situ, as well as invasive ductal carcinoma. Methods Immunohistochemistry was used to detect the expression of CCR7 and VEGF-D protein in the nomal breast tissue (n=20), slight and moderate ductal atypical hyperplasia tissue (n=20), severe atypical hyperplasia and intraductal carcinoma in situ tissue, as well as invasive ductal breast carcinoma tissue (n=73). In addition, the D2-40 staining was also used to determine lymphatic microvessel density (LMVD). Meanwhile, the relationship between the expression of the two kinds of protein and clinicopathological factors/LMVD was analyzed by statistical analysis in breast cancer, and the correlation between expression of CCR7 protein and expression of VEGF-D protein was analyzed too. Results ①The positive rates of CCR7 protein (χ 2 =23.905，P<0.050) and VEGF-D protein (χ 2 =22.349，P<0.050) were gradually increased in the normal breast tissue group 〔CCR7 protein: 0 (0/20), VEGF-D protein: 5.0% (1/20)〕, slight and moderate atypical hyperplasia group 〔CCR7 protein: 5.0% (1/20), VEGF-D protein: 20.0% (4/20)〕, severe atypical hyperplasia and intraductal carcinoma in situ group 〔CCR7 protein: 30.0% (6/20), VEGF-D protein: 40.0% (8/20)〕, and invasive ductal carcinoma group 〔CCR7 protein: 47.9% (35/73), VEGF-D protein: 57.5% (42/73)〕. ②The LMVD value gradually increased in normal breast tissue group (2.00±1.02), slight and moderate atypical hyperplasia group (6.70± 3.48), severe atypical hyperplasia and intraductal carcinoma in situ group (9.01±2.13), as well as invasive ductal carcinoma group (16.32±4.07), there was significant difference between any 2 groups (P<0.050). ③The expressions of CCR7 protein and VEGF-D protein were correlated with clinical staging, histological grading, lymph node metastasis, and expression of human epidermal growth factor receptor-2 (HER-2) protein in patients with breast cancer (P<0.050), the higher positive rates of CCR7 and VEGF-D protein occurred in patients with higher histological grading, later clinical staging of Ⅲ+Ⅳ (compared with staging of Ⅰ+Ⅱ), lymph node metastasis (compared with no lymph node metastasis), and positive expression of HER-2 protein (compared with negative expression of HER-2 protein). The result indicated that LMVD value was related with expression of VEGF-D protein (r=0.623, P<0.010) in patients with breast cancer, but there was no correlation with expression of CCR7 protein (r=-0.303, P>0.050). Furthermore, there was weak positive correlation between expression of CCR7 protein and expression of VEGF-D protein in breast cancer (r=0.112, P<0.050). Conclusion The results strongly suggest that the expression levels of the VEGF-D protein and CCR7 protein indicate the potential of translation some extent, and they play an important role in the progression of breast cancer.
Objective To detect expressions of CD31 and D2-40 in patients with simultaneous colorectal cancer with peritoneal metastasis and investigate their correlation between them. Method The expressions of CD31 and D2-40 protein in these 59 cases (there were 19 and 40 patients with or without peritoneal metastasis, respectively) of colorectal cancer were detected by immunohistochemical MaxVision method. Results ① The positive rates of CD31 and D2-40 protein expression in the colorectal cancer tissues with or without peritoneal metastasis were significantly higher than those of the normal colonic tissues (P<0.05), but which had no significant differences between the colorectal cancer tissues with or without peritoneal metastasis (P>0.05). ② The CD31 microvessel density (CD31-MVD) and D2-40 lymphatic microvessel density (D2-40-LMVD) in the colorectal cancer tissues with peritoneal metastasis were significantly higher than those of the normal colonic tissues (P<0.05) and the colorectal cancer tissues without peritoneal metastasis (P<0.05). ③ The CD31-MVD and D2-40-LMVD were not associated with all the clinicopathologic characteristics of the colorectal cancer patients without peritoneal metastasis (P>0.05), but which in the poorly differentiated adenocarcinoma and mucinous and signet ring cell carcinomas patients with peritoneal metastasis were significantly higher than those of the other types (P<0.05) and were not associated with the age, gender, and diamter of the tumor of it (P>0.05). ④ There was a positive correlation between the CD31-MVD and the D2-40-LMVD in the colorectal cancer patients with or without peritoneal metastasis (r=0.342, P=0.012; r=0.119, P=0.008). Conclusions CD31-MVD and D2-40-LMVD in colorectal cancer patients with peritoneal metastasis highly express and has a positive correlation, which means that they might have a certain relationship with peritoneal metastasis. There may be some common regulation way and collaboratively participate peritoneal metastasis of colorectal cancer.