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Lymphatic metastasis in epithelial ovarian carcinoma with respect to clinicopathological variables.

OBJECTIVE: The purpose of this study was to evaluate the prognostic factors, and the patterns of lymphatic metastasis in EOC patients who were treated with systematic pelvic and paraaortic lymphatic dissection. METHODS: A total of 420 EOC patients was retrospectively evaluated. Clinical factors available were evaluated for a possible significance in terms of lymphatic metastasis and paraaortic involvement. RESULTS: Two-hundred and three patients were found to have lymphatic metastasis. In multivariable analysis, stage (P < 0.001), histology (P < 0.01 for serous; P = 0.02 for mixed, and P = 0.04, for Brenner), and Ca-125 level higher than 500 U/ml (P = 0.04) were found to be significantly related with the lymphatic involvement. Age and grade were significant factors for paraaortic metastasis both in univariable and multivariable analysis (P = 0.003 and P = 0.02, respectively). Most of the patients with unilateral tumors had contralateral pelvic and/or paraaortic metastasis. There were eleven patients with lymphatic metastasis in stage I-II disease, and five had paraaortic metastasis while an additional five patients had contralateral pelvic nodal metastasis. However, there was no lymphatic involvement in Stage IA, Grade I-II disease (0/63). Survival analysis revealed no significant difference by the number of metastatic lymph nodes. CONCLUSION: In multivariable analysis, lymphatic involvement was predicted independently by stage, histology, and Ca-125 level. In apparently stage I-II disease, a considerable part of patients were upstaged due to lymphatic involvement. Although routine systematic lymphadenectomy is suggested for patients with early stage disease, further series are needed for a definite regimen in patients with stage IA G1-2 disease since we did not detect any lymphatic involvement in this unique group.

Adult↗

[Lymphatic metastasis in central direction and bowel axial direction in colonic cancers].

485 lymph nodes were founded by palpation in 44 R3 resected specimens of colonic cancers. In the bowel axial direction, the rate of lymphatic metastasis was 6.8%, which accound for 9.6% of the positive lymph node metastasis. All these positive nodes were limited from 10 cm proximal to 5 cm distal to the tumor. In the central direction, the rate of mesenteric lymphatic metastasis was 20.4%, and the rate of lymphatic metastasis at the root of mesentery was 4.5%, which accounted for 38.1% of the positive lymph node metastasis. Compared to the bowel axial direction, mesenteric lymphatic metastasis in the central direction was more common and should be carefully disseted during radical operation.

Adenocarcinoma↗

[Correlation between expression of vascular endothelial growth factor-C in tumor-associated macrophages and lymphatic metastasis in oral cancer].

BACKGROUND & OBJECTIVE: Previous study shows that both vascular endothelial growth-C (VEGF-C) and tumor-associated macrophages (TAMs) are related to lymphatic metastasis. This study aimed to explore the correlation between the expression of VEGF-C in TAMs and lymphatic metastasis in human oral squamous-cell carcinoma (OSCC). METHODS: After immunohistochemical staining, light microscope was used for counting macrophages and automated image analysis quantification was used to determine VEGF-C expression,which was reflected by positive index (PI). In addition,the double staining was also used to determine VEGF-C expression in TAMs. RESULTS: VEGF-C expression was higher in lymphatic metastasis group (PI=12.169+/-2.778) than in no-metastasis group (PI=8.498+/-2.674, P< 0.05). TAMs counts was related to VEGF-C expression in OSCC (r=0.370, P< 0.05). The result of double staining indicated that macrophage with positive VEGF-C expression accounted for about 22.8% of the total. CONCLUSION: Not only tumor cells but also TAMs secrete the VEGF-C in OSCC, and TAMs may play a major role in peritumoral lymphatic neoangiogenesis and lymphatic metastasis.

Antigens, CD↗

[Lymphatic metastasis and VEGF-C expression in ovarian epithelial tumors].

The aim of the present study was to explore the role of vascular endothelial growth factor-C (VEGF-C) in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign cystadenomas. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density (MVD) were assessed by image analysis. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than that in borderline tumors and benign cystadenomas (p < 0.05 or p < 0.01). In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage III-IV and with lymphatic metastasis than those of clinical stage I-II and without lymphatic metastasis respectively (p < 0.05 or p < 0.01), VEGFR-3 positive vessels and MVD was significantly higher in the VEGF-C protein positive tumors than negative tumors (p < 0.05), VEGFR-3 positive vessels was significantly correlated with MVD(p < 0.01). These data suggest that VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian carcinomas, and VEGF-C could be used as a biologic marker of metastasis in ovarian epithelial carcinomas.

Adult↗

[Hemorheological study on the process of tumor invasion and lymphatic metastasis].

Mouse transplantable hepatoma (H22) was used as an experimental model for lymphatic metastasis. The tumor cells were transplanted subcutaneously into right footpads of inbred 615-strain mice. The hemorheological changes during invasion and lymphatic metastasis in mice were observed. The results of histological examination showed that tumor invasion was divided into early, middle and late invasive stages, and the metastasis was divided into early, middle, late and final metastasis periods. Tumor invasion began 3 days after tumor transplantation, and the late stage of invasion was found at 9 days. Metastasis began 6 days after transplantation; at 19 days metastasis to lymph nodes in the right side reached grade IV. Metastasis to lymph nodes in the left side appeared 14 days after tumor transplantation. In the early and middle invasive stages only plasma viscosity increased significantly, while other hemorheological values were unchanged. The blood viscosity and aggregation of red blood cells decreased significantly after the metastatic late stage. The hematocrit of red blood cells began to decrease in the final stage of metastasis, and in the meantime, the rigidity of red blood cells began to increase, while plasma viscosity showed no changes after the late metastatic stage. The results and mechanism of hemorheological changes are discussed.

Animals↗

[cDNA microarray in the gene expression pattern in lymphatic metastasis of pancreatic carcinoma].

OBJECTIVE: Analysis of differential gene expression profiles by cDNA microarray in pancreatic carcinoma with or without lymphatic metastasis. METHODS: cDNA microarray was prepared by spotting polymerase chain reaction (PCR) products of 4 000 human genes onto specially treated glass slides. The cDNA probes were prepared by labeling normal tissue mRNA and cancer tissue mRNA with Cy3-dUTP and Cy5-dUTP, separately through reverse transcription. The mixed probes were, then, hybridized to the cDNA microarray. The chips were scanned by ScanArray 3000 laser scanner (General Scanning, Inc) on two wavelengths. The acquired image was analyzed by ImaGene 3.0 software (BioDiscovery, Inc). The intensity of each spot on the two wavelengths represented the quantity of Cy3-dUTP and Cy5-dUTP, with Cy5 to Cy3 ratio computed on each. RESULTS: Fifty-six genes (including 24 previously reported) exhibited differential expressions in 2 specimens of pancreatic carcinoma with lymphatic metastasis and 2 without. CONCLUSION: cDNA microarray provides an promising approach to specific gene expressions of the presence of lymphatic metastasis in human pancreatic carcinoma.

Aged↗

The functional SNP in the matrix metalloproteinase-3 promoter modifies susceptibility and lymphatic metastasis in esophageal squamous cell carcinoma but not in gastric cardiac adenocarcinoma.

The matrix metalloproteinases (MMPs), a family of proteolytic enzymes that degrade different components of the extracellular matrix, play important roles in tumor development and invasion. A single adenine insertion/deletion polymorphism (6A/5A) in the MMP3 promoter region causes transcriptional elevation. The aim of this study was to assess the effects of this single nucleotide polymorphism (SNP) on the development and clinical staging of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). The MMP3 SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 417 cancer patients (234 ESCC and 183 GCA) and 350 controls in north China. The overall distribution of the MMP3 SNP in ESCC and GCA patients was not significantly different from that in healthy controls. However, smoking individuals with the 5A/5A or 5A/6A genotype were significantly more common in ESCC patients than in controls (37.5 versus 23.3%, xi(2) = 5.13, P = 0.02). Thus, smokers with at least one 5A allele had a significantly increased risk of ESCC, compared with 6A homozygotes (age and sex adjusted OR = 1.95, 95% CI = 1.08-3.53). The significant difference in the SNP distribution between ESCC patients, GCA patients and controls was not observed when stratified by family history of upper gastrointestinal cancer. In addition, the frequency of the 5A/5A + 5A/6A genotypes in ESCC patients with and without lymphatic metastasis was significantly different (45.8 versus 27.8%, xi(2) = 4.56, P = 0.03). Therefore, patients with at least one 5A allele were significantly more prone to lymphatic metastasis of ESCC. In contrast, no significant difference in the SNP distribution between patients with and without lymphatic metastasis was observed in GCA. The present study suggests that the MMP3 promoter SNP might be associated with a risk of development and lymphatic metastasis in ESCC but not in GCA.

Adenocarcinoma↗

Studies on lymphatic metastasis. I. Primary immunoregulatory role of regional lymph nodes in the establishment of lymphatic metastases.

The growth of syngeneic ascites MM48 tumor cells implanted in a hind footpad of a C3H/He mouse slowed at 10-12 days after tumor implantation. At that time, no killer activity was detected in all lymphoid organs examined, including regional lymph node. However, positive immunoregulatory activity, i.e., killer-augmenting activity, which was assessed by cytotoxicity assay with tumor-specific immune cytotoxic T-cells, was detected primarily in the regional lymph node. In contrast, local preimmunization with larger doses of irradiated tumor cells enhanced growth of subsequently challenged tumor and lymphatic metastasis. In the regional node of preimmunized tumor bearer, negative immunoregulatory activity, i.e., killer-suppressing activity, was induced. Both immunoregulatory activities were tumor specific and resided in Lyt-1+ T-cells. Tumor-specific immunoregulatory activity seemed to be related to tumor dose used for challenge, whether positive or negative immunoregulatory activity was induced. Lymphatic metastases examined by bioassay and histologic examination were evaluated with reference to immunoregulatory activity that appeared in the regional lymph node during tumor development. The incidence of tumor detection in the node by bioassay was decreased when killer-augmenting activity was present there. Proliferation of metastatic tumor cells judged by microscopic observation was in parallel with suppressor activity generated in the node.

Animals↗

Differential metastasis-associated gene analysis of prostate carcinoma cells derived from primary tumor and spontaneous lymphatic metastasis in nude mice with orthotopic implantation of PC-3M cells.

The purpose of these studies was to explore the genes associated with invasion and metastasis of human prostatic carcinoma line PC-3M in nude mice. After PC-3M cells were inoculated in orthotopic site (prostate) in male nude mice for two months, tumor cells were isolated from primary tumor and lymph node metastasis in the same mouse, respectively. Cell invasion and adhesion ability in vitro were first compared between two cell lines. Then human metastasis-related genes differentially expressed between them were analyzed by utilizing cDNA microarray technique. The in vitro cell invasion and adhesion potential of tumor cells from lymph node metastasis was significantly higher than those from primary tumor, Metastasis-related genes differentially expressed between those two cell lines were identified, all of them were up-regulated in the tumor cells from lymph node metastasis and could be categorized as: (1) genes encoding cellular matrix-degrading proteolytic enzyme including cathepsin and MMP; (2) genes encoding transcription factors; (3) genes related to heterotypic adhesion of tumor cells; (4) genes encoding cell surface receptors. Moreover, Four genes were chosen for semi-quantitative RT-PCR analysis, they showed a consistent expression pattern with that of cDNA microarray analysis. We concluded that the lymph node metastasis in nude mice given an injection of PC-3M cells in the prostate is a selective process favoring the survival and growth of a special subpopulation derived from primary tumor with specific genetic alterations, which may play a pivotal role in the metastasis of prostate cancer. Identification and further characterization of these genes may allow a better understanding of lymphatic metastasis in prostate carcinoma.

Animals↗

[Zymographic analysis of matrix metalloproteinases in mouse carcinoma cell lines with different lymphatic metastasis potential].

OBJECTIVE: To investigate the correlation between lymphatic metastasis and matrix metalloproteinases (MMPs) activity. METHODS: Zymographic analysis was used to detect the difference of MMPs product and activities between high lymphatic metastatic cell line (HCa-F) and low lymphatic metastatic cell line (HCa-P), that were cultured in the medium including homogenate of lymph node or liver or spleen tissue. RESULTS: HCa-F and HCa-P cells produced small quantities of MMP-9 in 1640 medium. After adding lymph node homogenate to the culture medium, F cells produced a large quantity of MMP-9 as well as active MMP-9 and MMP-2. P cells also produced MMP-9, active MMP-9 and MMP-2, but were much lower than that of F cells. Neither F cells nor P cells produced MMPs in the media with homogenate of liver or spleen added. CONCLUSION: The metastatic potential of F cells is stronger than that of P cells may be due to F cell's ability to secrete MMPs is stronger than P cell's, therefore the production of MMPs of hepatocarcinoma cells is closely correlated to their metastatic potential.

Animals↗

[Screening of differentially expressed genes in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis].

OBJECTIVE: To screen genes differentially expressed in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis. METHODS: A subtracted cDNA library of mouse hepatocarcinoma cell line with high potential of lymphatic metastasis Hca-F and its synogenetic cell line Hca-P with low metastatic potential was constructed by suppression subtractive hybridization (SSH) method. The screened clones of the subtracted library were sequenced and GenBank homology search was performed. RESULTS: Ten differentially expressed cDNA fragments of Hca-F with high potential of lymphatic spreading were obtained, two of which were newly identified ones. CONCLUSION: SSH is a useful technique to detect genes of differential expression and an effective method to clone novel genes.

Animals↗

[Impacts of clinicopathologic parameters on lymphatic metastasis of oral squamous cell carcinoma].

OBJECTIVE: To evaluate the effects of clinicopathologic parameters on lymphatic metastasis of oral squamous cell carcinoma. METHODS: One hundred and ninety-three patients who underwent therapy in our department were included in this study. Ten parameters (T and N stages, location, patterns of invasion, thickness, lymphocyte infiltration, karyokinesis count, degrees of differentiation, degrees of cell keratinization and nuclear polymorph) were evaluated to determine their effects on lymphatic metastasis of oral carcinoma using univariate and multivariate analysis. RESULTS: By using the univariate analysis, five parameters (T and N stage, pattern and depth of invasion, lymphocyte infiltration) showed significant impacts on pathologic nodal metastasis. From multivariate analysis, however, only patterns of invasion were independent predictors of metastasis. Also, patterns of invasion were the only significant factors that influence the post-operative metastasis besides pattern of neck treatment. CONCLUSION: The pattern of invasion is the most important parameter that influences the metastasis of oral squamous cell carcinoma.

Adult↗

[Detection of Epstein-Barr virus gene in nasopharyngeal carcinoma with neck lymphatic metastasis].

OBJECTIVE: To investigate the presence of Epstein-Barr virus(EBV) gene in neck lymphatic metastasis of nasopharyngeal carcinoma. METHODS: Fifty patients' masses in the neck were punctured and the fluids were analyzed with PCR for EBV DNA. RESULTS: Twenty seven cases showed EBV DNA positive among thirty cases of nasopharyngeal carcinoma with neck lymphatic metastasis, and the positive rate was 90%. One case was EBV DNA positive in seven cases of malignant lymphoma and the positive rate was 14.3%. One case was EBV DNA positive in eight tumor patients without NPC metastasis and the positive rate was 12.5%. Five cases with nasopharyngeal inflammation and neck lymphatic node proliferation were demonstrated to be EBV DNA negative. CONCLUSION: This technique is rapid, sensitive and specific, which is valuable clinically, especially for the diagnosis in patients with cryptic nasopharyngeal carcinoma and with neck metastasis but lack of clear original focus.

Adolescent↗

[Colorectal cancer: lymphatic metastasis and choice of operation].

OBJECTIVE: To study lymphatic metastasis of colorectal cancer for deceding the of dissection extent of dissection. METHODS: Six hundred and twenty-three lymph nodes from 74 cases of colorectal cancer were analyzed after D(3) resection. They were classified into peritumor, longitudinal spread, and upward spread groups. The metastasis rate of lymph node and its incidence were calculated. RESULTS: The metastasis rate of lymph node and its incidence in the peritumor, longitudinal spread, and upward spread (N(2) and N(3)) groups were 47.2% and 38.6%, 22.8% and 18.6%, and 29.7% (20.3% and 9.4%) and 10.2% (19.0% and 5.3%), respectively. The distribution rate of metastatic lymph node was 61.2%, 17.1%, and 21.6% in the peritumor, longitudinal spread, and upward spread groups, respectively. Within 2.0 cm on the anal side of rectal cancer, the metastasis rate was 3.7%, whereas in 2.0 - 4.0 cm no metastasis was observed cancer at the lower part of the rectum demonstrated a higher lateral metastasis rate. CONCLUSIONS: Colorectal cancer tends to metastasize to longitudinal and the risk of metastasis increased in the stage of pT(3) and pT(4) or low differentiation stage. Jump metastasis is also a feature. D(3) radical resection is necessary for colorectal cancer, but extended lateral lymph node needs enectomy or total mesorectal excision. No residual tumor tissue exists at the anastomosis site after low anterior resection when the excision distance is beyond 2.0 cm from the anal margin of rectal cancer.

Adult↗

Relationship between lymph node sinuses with blood and lymphatic metastasis of gastric cancer.

AIM: To elucidate the relationship between lymph node sinuses with blood and lymphatic metastasis of gastric cancer. METHODS: Routine autopsy was carried out in the randomly selected 102 patients (among them 100 patients died of various diseases, and 2 patients died of non-diseased reasons), their superficial lymph nodes locating in bilateral necks (include supraclavicle), axilla, inguina, thorax, and abdomen were sampled. Haematoxylin-Eosin staining was performed on 10 % formalin-fixed and paraffin-embedded lymph node tissue sections (5 um). The histological patterns of the lymph sinuses containing blood were observed under light microscope. The expression of CD31, a marker for endothelial cell, was detected both in blood and non-blood containing lymph node sinuses with the method of immunohistochemistry. RESULTS: Among the 1 322 lymph nodes sampled from the autopsies of 100 diseased cases, lymph node sinuses containing blood were found in 809 lymph nodes sampled from 91 cases, but couldn't be seen in the lymph nodes sampled from the non-diseased cases. According to histology, we divided the blood containing lymph node sinuses into five categories: vascular-opening sinus, blood-deficient sinus, erythrophago-sinus, blood-abundant sinus, vascular-formative sinus. Immunohistochemical findings showed that the expression of CD31 was strongly positive in vascular-formative sinuses and some vascular-opening sinuses while it was faint in blood-deficient sinuses, erythrophago-sinuses and some vascular-opening sinuses. It was almost negative in blood-abundant sinus and non-blood containing sinus. CONCLUSION: In the state of disease, the phenomenon of blood present in the lymph sinus is not uncommon. Blood could possibly enter into the lymph sinuses through the lymphaticovenous communications between the veins and the sinuses in the node. Lymph circulation and the blood circulation could communicate with each other in the lymph node sinuses. The skipping and distal lymphatic metastasis of gastric cancer may have some connection with the blood containing lymph node sinuses.

Adolescent↗

[Lymphatic metastasis of breast cancer and selection of operation].

Studies of 169 cases of breast carcinoma showed that lymphatic metastasis was closely related to biological behavior of the cancer. Modified radical operation or modified extended radical operation were performed in cases of TNM stage I and II by pre- and intraoperative estimation of the tumor less than or about 5 cm in diameter, limited within mammary gland, and of expansion type. Histological typing and grading, degree of infiltration, condition of ER and lymphatic metastasis were used to plan postoperative adjuvant therapy. The importance of investigation of ER status of the lesions lies in proper arrangement of combined therapy and prediction of prognosis.

Adult↗

Tumor cell adhesion to frozen lymph node sections--a correlate of lymphatic metastasis in breast carcinoma models of human and rat origin.

The role of tumor cell adhesion in lymphatic metastasis of breast cancer was investigated in vitro using a rat mammary carcinoma model of four cell lines with different metastatic phenotypes, two human breast cancer cell lines, and cryostast sections of normal rat or human lymph nodes, respectively. A positive correlation was found between the adhesion levels obtained with three metastatic rat mammary cell lines (TMT-081 greater than MT-100M & TMT-50) and a non-metastatic line MT-W9B, the latter being 3-4 fold less adhesive to the lymph node sections than the metastatic tumors. This selective adhesion was specific, as it was not found with cryostat sections of rat liver and brain. Enzyme assays indicated that cell surface glycoproteins bearing terminal beta-galactoside residues were involved in the adhesion of the rat tumors. Adhesion of the human breast carcinoma cells Hs578T to sections of human lymph nodes was significantly higher than that of the normal breast epithelial cell line Hs578Bst, and comparable to adhesion of a second breast carcinoma line, MCF-7. Moreover, Hs578T cells isolated from regional lymph nodes of tumor-bearing nude mice were significantly more adhesive to human lymph node sections than the parental line. Adhesion of both human and rat tumors could be partially blocked by the addition of the synthetic peptide GRGDSPK and by antibodies directed to the beta 1 chain of integrin, suggesting that an integrin receptor may played a role in the adhesion. The results suggest that tumor cell adhesion to cryostat sections of lymph nodes is a correlate of the malignant phenotype in mammary tumors of diverse origins, and could be used to delineate the adhesion factors mediating lymphatic metastasis.

Animals↗

[A model of nasopharyngeal carcinoma with spontaneous highly lymphatic metastasis in nude mice and its biological characteristics].

OBJECTIVES: To establish a model of nasopharyngeal carcinoma with spontaneous highly lymphatic metastasis in nude mice and to study its biological characteristics. METHODS: The clone cells of nasopharyngeal carcinoma(NPC), CNE-2Z-H5, were inoculated into nude mice. The cancer cells of lymph node metastatic foci were transplanted into nude mice again when the metastasis of nude mice were observed. After repetition of this procedure for 9 cycles, the metastatic rate and the metastatic paths were observed in nude mice of every passage; The changes were also observed in proliferation ability, expression of growth factor and its receptor in vitro, proliferation index(PI), and tumor weight and doubling time of the transplantable tumor in every passage in vivo. RESULTS: The lymphatic metastatic rates were higher than 85%. The metastatic paths were single, the proliferation ability was increased in cancer cells of every passage in vivo and vitro after passaging cancer cells of lymphatic metastatic foci for 9 cycles in nude mice. CONCLUSIONS: A model of nasopharyngeal carcinoma with spontaneous highly lymphatic metastasis has been established in nude mice, and the possibilities of metastasis and proliferation are increased after progression of NPC cells in nude mice. There is a close relationship between the metastasis and proliferation in NPC.

Animals↗