ObjectiveTo investigate the expression of tumor metastasis associated genes-1 (MTA1) and vascular endothelial growth factor-C (VEGF-C) in esophageal squamous cell carcinoma (ESCC) and the relationship between them and lymphangiogenesis. MethodA total of 107 patients who received excision for ESCC in the Cardiothoracic Surgery Department of Suining Central Hospital from March 2013 through January 2014 were enrolled. And the paraffinembedded esophageal tissues in 56 healthy persons were collected. The expression of MTA1 and VEGF-C in ESCC was detected using the immunohistochemical method. And D2-40 was used to label the micro-lymphatic endothelial cells of the tumor tissues while the micro-lymphatic vessel density (LVD) was counted. Meanwhile, a statistical analysis was performed for the relationship between MTA1 with VEGF-C and clinical pathological parameters. ResultsThe expression rates of MTA1 protein and VEGF-C protein in ESCC (50.4% and 58.8%, respectively) were higher than those in normal esophageal tissues with a statistical difference (P<0.05). Besides, their high expression rates in stage T3/T4 ESCC and lymph node metastasis group were significantly higher than those in stage T1/T2 ESCC and metastasisfree group, with statistical differences (P<0.05). The high expression rates of MTA1 and VEGF-C protein in ESCC with different TNM stages were compared using Kruskal-Wallis test with statistical differences (P<0.05). Moreover, a positive correlation existed in the expression level between MTA1 protein and VEGF-C protein of ESCC (Spearman coefficient r=0.512, P=0.000). And LVD of the high expression group for MTA1 protein and VEGF-C protein was statistically different from that of the low expression group (P<0.05). ConclusionThe expression of MTA1 is positively correlated with the expression of VEGF-C in ESCC. And they may co-promote lymphangiogenesis and lymphatic metastasis in ESCC. Therefore, both can be used as the laboratory indicators to determine the prognosis of ESCC.
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.
【Abstract】Objective To introduce the current studies of the role of vascular endothelial growth factorC (VEGFC) and VEGFD in lymphangiogenesis and lymph node metastasis of gastrointestinal neoplasma. Methods The related literatures in recent 5 years were reviewed. Results The growth factors VEGFC and VEGFD enhance lymphangiogenic metastasis of gastrointestinal neoplasma with the property of angiogenesis and lymphangiogenesis. In gastric adenocarcinoma, VEGFC mRNA and tissue protein expression correlate with lymphatic invasion, lymph node metastasis, venous invasion and reduced 5year survival rates. The role of VEGFC in esophageal squamous cancer and colorectal cancer and VEGFD in colorectal cancer is not certain, with conflicting reports in the published literatures.Conclusion The VEGFC, VEGFD/VEGFR3 signal pathway may become the ideal target for inhibition of tumor proliferation and metastases, antilymphangiogenesis therapy may be a novel potential strategy in tumor biological therapy.
ObjectiveTo investigate the relationship between vascular endothelial growth factor receptor-3 (VEGFR-3) and clinical pathology of gastric carcinoma(GC).MethodsThe expression of VEGFR-3 in 80 GCs and 20 gastric benign tissues (GBT) was detected by immunohistochemistry(SP), by which the density of lymphatic vessels (DLV) was calculated. ResultsThe DLV in GC was （5.800 0±2.318 9）/×200, in GBT （2.380 0±0.462 9）/×200(P=0.000); in GC with lymph node metastasis （6.948 3±1.583 1）/×200, without lymph node metastasis （2.772 7±0.428 9）/×200 （P=0.000）. In poorly differentiated type group, DLV was （7.681 8±0.982 9）/×200, higher than that in moderately and highly differentiated type group 〔(3.500 0±1.028 2）/×200, P=0.000〕. DLV in pTNM Ⅰ+Ⅱ was （4.291 7±1.688 0）/×200, in Ⅲ+Ⅳ （8.062 5±0.759 4）/×200 （P=0.000）.ConclusionDLV shows positive relations with pTNM stage, differentiation and lymph node metastasis of GC.
Lymphangiogenesis plays an active role in lung cancer metastasis. Currently, it attracts more and more attention because of its role in tumor metastasis and become a hotspot in the field. Lymph node metastasis of lung cancer is the key factor for the unfavourable prognosis of the patient suffered lung cancer. But the correlation of lymphangiogenesis and lung cancer metastasis is yet unknown. Some development about it is reviewed.
Objective To reveal the significance of D2-40/CK19 dual immunohistochemistry for micrometastasis of peripancreatic neural plexus in patients with pancreatic cancer. Methods Between January 2006 and January 2007, 44 patients with pancreatic duct adenocarcinoma underwent extended radical resection. Conventional hematoxylin/eosin staining and double immunohistochemical staining using CK19 and D2-40 were used to determine peripancreatic neural invasion and lymphatic vessel invasion (LVI) in peripancreatic neural plexus tissues. Results D2-40 immunohistochemistry showed brown-yellow tube-like lymph vessels. The lymph vessel of peripancreatic nerve plexus followed vascular and perineurium, and the lymph vessel adjacent to peripheral nerve fascicles owned tube-like structure. CK19 immunohistochemistry showed cytoplasm of pancreatic cancer cell was red. The LVI was observed in lymphatic capillaries. Peripancreatic neural plexus invasion was found in 30 cases (68.2%), tumor cell invading presented in lymph vessels of peripancreatic neural plexus in 21 patients (47.7%) with pancreatic cancer. The peripancreatic neural plexus invasion was associated with LVI (P=0.003). The plexus of pancreatic capitalis and celiac plexus were respectively confirmed to be the spot with the highest lymphatic vessel density and the maximal incidence of neural plexus invasion simultaneously. Conclusions Patients with pancreatic cancer should be given the opportunity of radical operation combining related peripancreatic neural plexus as far as possible. The dual immunohistochemical staining with anti-CK19 and anti-D2-40 monoclonal antibodies should be a new method in research of perineural invasion of pancreatic cancer, exhibiting both the pancreatic cancer cells and lymph vessels clearly and distinctly.
【Abstract】Objective To understand the features of lymphatic vessel, and to summarize the foundation and mechanism of the promotion and inhibition of tumor lymphangiogenesis recorded on the current studies of animal experiments and clinical researches. Methods The related literatures of the structural features of lymphatic vessel, lymphatic endothelial molecular markers, the origin of lymphatic tumors, the molecular mechanisms and regulatory factors were reviewed, and the relationship between tumor lymphangiogenesis and lymphatic metastasis, the treatment targeting at the formation of the anti-tumor lymphatic vessel and its existing problems were also analyzed. Results Hyperplasia of lymphatic vessels occurred during the process of tumor formation and progression. The structural features of the lymphatic vessels in the tumor were conducive to tumor lymphatic metastasis. In recent years, methods of anti-lymphangiogenesis and inhibition of tumor lymphatic metastasis had achieved considerable success in animal experiments. However, there were still a lot of problems need to be solved. Conclusion Tumor lymphangiogenesis has a significantly positive correlation between tumor lymphatic metastasis and patients’ prognosis, which may indicate that treatment against the formation of tumor lymphatic vessel maybe effective.