10894

LYVE1

lymphatic vessel endothelial hyaluronan receptor 1;LYVE1;lymphatic vessel endothelial hyaluronan receptor 1

cell surface retention sequence binding protein-1|cell surface retention sequence-binding protein 1|extracellular link domain containing 1|extracellular link domain-containing 1|extracellular link domain-containing protein 1|hyaluronic acid receptor|lymph

11p15

protein-coding

BACKGROUND: Early colorectal cancer (ECC) is curable by endoscopic local resection; however, 10% of patients with ECC exhibit lymph node (LN) metastasis. In the current study, accurate predictors for LN metastasis in patients with ECC were examined by using immunohistochemistry with the lymphatic endothelial hyaluronan receptor 1 (LYVE-1) antibody to discriminate between lymphatics and blood vessels. METHODS: Colorectal tissue specimens obtained from 71 patients with ECC, including 28 patients with regional LN metastasis, were immunostained with antibodies against LYVE-1, beta-catenin, claudin-3, claudin-4, and cytokeratin. The significance of the histopathologic variables for LN metastasis in ECC was investigated on the basis of specific histopathologic parameters. RESULTS: Lymphatic invasion confirmed by LYVE-1 immunohistochemistry was observed mainly in the submucosal area around the primary tumor and rarely was observed in the tumor. expression patterns of beta-catenin, claudin-3, and claudin-4 in cancer cells at the invasive front were irrelevant to LN status. tumor size, depth of invasion, histologic tumor type, budding formation, and lymphatic invasion were statistically significant to LN status in univariate analysis; however, only 2 factors--lymphatic invasion and budding formation at the invasive front-were independent predictors of LN metastasis in ECC. CONCLUSIONS: LYVE-1 immunohistochemistry appeared to be a useful method for detecting lymphatics invaded by cancer cells, and detailed examination of the submucosa around the tumor may be important for predicting LN metastasis. When lymphatic invasion and budding formation are observed histopathologically in patients with ECC, additional therapy, such as adjuvant chemotherapy or a curative resection of the regional LN, may be required.

AIM: To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their levels and clinicopathological parameters in gastric cancer. METHODS: Tissue samples were obtained from 33 patients (8 females) with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry. RESULTS: LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic features such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the distribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining. CONCLUSION: LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.

OBJECTIVE: To study the relationship between density, location, proliferation of lymph vessels and clinicopathological features of laryngeal squamous carcinoma. METHOD: tumor lymph vessels were quantitated and located in archival specimens of laryngeal carcinoma by LSAB immunostaining for the recently described lymphatic endothelial marker LYVE-1. The Ki67 proliferation marker was used to evaluate the proliferating conditions of LYVE-1(+) vessels with EnVision immunohistochemical methods. RESULT: (1) The density of intratumoral LYVE-1(+) vessels was higher in the cases of neck lymph nodal metastasis group than that of no neck lymph nodal metastasis group (P = 0.000). There was a significant difference of the density of intratumoral LYVE-1(+) vessels in the cases of T1, T2 and T(3-4) group. There was no significant difference of the density of intratumoral LYVE-1(+) vessels between supraglottic group and glottic group, squamous cell histological types I group and types II group (P = 0.125, 0.146, respectively). (2) The density of peritumoral LYVE-1(+) vessels was higher in the cases of neck lymph nodal metastasis group than that of no neck lymph nodal metastasis group. However,there was no statistic significance (P = 0.253). (3) Ki67(+) immunostaining occurs in some of the intratumoral LYVE-1(+) vessels, interestingly, there was no this phenomenon in the peritumoral LYVE-1(+) vessels. CONCLUSION: Intratumoral lymph vessel density marked by LYVE-1 in laryngeal carcinoma was significantly correlated with tumor infiltration and metastasis. Our results provide potent evidence that proliferating lymphatics exists in intratumoral areas of laryngeal carcinoma mainly which maybe contribute to lymph node metastasis in some cases.

OBJECTIVE: To investigate the expression of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), the homeobox gene (Prox-1), in patients with non-small cell lung cancer (NSCLC), the relationship with microlymphatic vessel density, lymph node metastasis and their clinic pathological value. METHODS: Forty specimens of the NSCLC as experimental group and eleven pulmonary benign diseases as control group were studied. The expressions of LYVE-1, Prox-1 and CD31 protein in specimens of NSCLC and normal pulmonary tissue were studied with immunohistochemical (IHC) technique. Microlymphatic vessel density (MLVD) and microvessel density (MVD) were counted. Meanwhile, all specimens were also examined by conventional pathological method. Clinicopathological data of each patient were recorded and analyzed. RESULTS: (1) Among 40 cases of the center of NSCLC cancerous tissues, the MLVDs marked by LYVE-1 and Prox-1 were 4.22 +/- 1.25 and 1. 99 +/- 1.49 respectively, which were significantly lower than those of the pulmonary benign diseases tissues (P = 0.00). (2) The MLVDs marked by LYVE-1 and Prox-1 in NSCLC cancerous invasive edge were 10.89 +/- 2.06 and 6.63 +/- 1.99 respectively, which were significantly higher than those in the center of cancerous tissues and those of the pulmonary benign diseases tissues (P = 0.000). (3) The MLVDs marked by LYVE-1 and Prox-1 in cancerous invasive edge were not correlated with age, gender, site and dimension of lesion, types of histological and degree of differentiation, but correlated significantly with lymph node metastasis (P = 0.000) and PTNM stage (P = 0.000). Meanwhile, along with lymph node metastasis and increasing of PTNM stage, the expressions of LYVE-1 and Prox-1 protein and MLVDs have significantly increased, but the microvessel density marked by CD31 in cancerous invasive edge was not correlated significantly with lymph node metastasis (P = 0.450) and PTNM stage (P = 0.377). (4) Significant correlation between LYVE-1 and Prox-1 (r = 0.529, P = 0.000) expression was observed in NSCLC; moreover, no correlations between LYVE-1 and CD31, Prox-1 and CD31 (r = 0.034, P = 0.837; r = -0.075, P = 0.647) were The functional microlymphatic vessels correlated with lymphatic metastasis are mainly observed. CONCLUSION: located in the cancerous invasive edge rather than the center of cancerous tissues. LYVE-1 and Prox-1 might be acted as molecular phenotypes of lymphangioghesis in NSCLC and as important markers for evaluating lymphatic metastasis and prognosis in patients with NSCLC.