Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although renal sinus vein invasion is the most common site of extrarenal involvement in clear cell renal cell carcinoma (CC), CC also spreads by lymphatics. As cortical lymphatics drain into the sinus, some involved sinus structures may be lymphatics, not veins. This possibility was investigated with podoplanin, a specific lymphatic endothelial marker, in 40 CC with sinus vein invasion. Ten blocks of uninvolved kidney, serving as controls, showed lymphatics within the adventitia of midcortical intralobular arteries. Lymphatics became more numerous and enlarged with progression towards the medulla. No lymphatics were among glomeruli or within the medulla unless associated with inflammation. The largest lymphatics occurred within the sinus, and were also noted within pelvic muscularis, and media of large veins. Intralymphatic tumor was observed and divided into two Groups. Group 1 (four cases) involved lymphatics within the invasive edge of tumors lacking a pseudocapsule. The lymphatics were small (0.045-0.19 mm), irregularly shaped, often incomplete, and contained single cells or small clusters of tumor cells. Group 2 (four cases) involved sinus lymphatics separate from tumor. One case each also involved adventitial lymphatics of an intralobular artery, the muscularis of the renal pelvis, and media of a muscular vein. The intralymphatic tumor in Group 2 often appeared discohesive, not endothelial cell invested, and larger than in Group 1 (0.4-0.5 mm). Conversely, tumor within muscular veins was cohesive, contained a capillary plexis, and was endothelial cell invested. In conclusion, intralymphatic tumor can be demonstrated in CC. Lymphatic involvement is less frequent than venous involvement and involves smaller structures. The potential for lymphatic spread may not be equal among involved lymphatics. Small peritumoral lymphatics may be destined for destruction by tumor growth. However, involved lymphatics within sinus and associated with renal pelvis, are likely sources for lymphatic spread and lymph node metastases.
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PMID:Renal lymphatics, and lymphatic involvement in sinus vein invasive (pT3b) clear cell renal cell carcinoma: a study of 40 cases. 1654 67

Lymphatic metastasis of tumor cells represents a series of extremely complex and sequential processes that include dissemination and invasion into surrounding stromal tissues from primary tumors, penetration into lymphatic walls and implantation in regional lymph nodes, and extravasation or proliferation in parenchyma of target organs. Recent developments in lymphatic biology and research, especially the application of unique molecular markers specific for lymphatic endothelial cells (LECs), LYVE-1, Prox-1 and podoplanin have provided exciting new insights into the tumor microenvironment and LEC-tumor cell interface. To date, established factors for determining the behavior and prognosis of primary tumors have been emphasized morphologically and physiologically, i.e., lymphatic impairment and vessel density, dysfunction of lymphatic valves, interstitial fluid pressure, as well as a series of lymphangiogenic growth factors including VEGF-C/-D, and other cytokines and chemokines. Increasing knowledge of the tumor biological significance in lymphatics within the tumors (intratumoral lymphatics, ITLs) and at the tumor periphery (peritumoral lymphatics, PTLs) has greatly promoted understanding of tumor access into the lymphatic system by inducing lymphangiogenesis or by co-opting preexisting lymphatics. Therefore, the targeting PTLs and ITLs, which have been proposed as an important route for antimetastatic approach, are deemed worthy of further study in various animal tumor models and human tumors.
Cancer Metastasis Rev 2006 Dec
PMID:Lymphatic endothelial cells, tumor lymphangiogenesis and metastasis: New insights into intratumoral and peritumoral lymphatics. 1716 Jul 13

Distinction of primary skin adnexal carcinomas from cutaneous metastasis of adenocarcinomas is challenging. In this study, we evaluated podoplanin immunoreactivity in a series of primary skin adnexal tumors and adenocarcinomas metastatic to skin using a D2-40 antibody. The initial test series were composed of a total of 93 cases including 32 primary skin adnexal carcinomas, 46 benign primary adnexal tumors, and 15 cutaneous metastatic adenocarcinomas. We found that variable D2-40 reactivity was seen in all of the primary cutaneous carcinomas including sebaceous carcinomas (10/10), squamous cell carcinomas (10/10), porocarcinomas (4/4), trichilemmal carcinomas (4/4), skin adnexal carcinomas not otherwise specified (4/4), and in the majority of benign skin adnexal tumors. In contrast, no podoplanin immunoreactivity was seen in any of the 15 (0/15) cutaneous metastases. To confirm the initial findings and to further explore the utility of podoplanin reactivity in the distinction of these tumors, we also examined a test set of 35 unknown cases, including 21 adenocarcinomas metastatic to skin and 14 primary adnexal tumors, in a blinded fashion. In this test set of cases, podoplanin was negative in 22 cases and positive in 13 cases. Of the 22 podoplanin negative cases, 20 were proven to be metastatic adenocarcinoma. Of the 13 D2-40 positive cases, 12 were proven to be primary adnexal tumors. Our results suggest that podoplanin can be a useful tool to distinguish primary skin adnexal carcinomas form adenocarcinomas metastatic to skin with high sensitivity (94.5%) and specificity (97.2%).
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PMID:Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin. 1725 77

In lung cancers, lymph node metastasis of cancer cells is one of the most important prognostic factors, and lymphatic vessel invasion (LVI) is very important in the stage preceding lymph node metastases. Recently, it has been reported that lymphatic vessel density (LVD) is associated with lymph node metastasis. The aim of the present study was to evaluate the relationship between LVD and LVI based on the immunohistochemical expression of podoplanin or D2-40, which are new specific markers for lymphatic endothelium. Using 76 cases of pulmonary adenocarcinoma, the relationship between LVD and LVI, lymph node metastases, vascular endothelial growth factor C (VEGF-C), VEGF-D or hepatocyte growth factor (HGF) expression was investigated. LVD was significantly associated with LVI, lymph node metastases and VEGF-D expression. LVI was also associated with lymph node metastases, histological subtype, VEGF-C or VEGF-D expression. High LVD, induced by VEGF-C or VEGF-D expression of cancer cells, is a good indicator of lymphatic metastases and LVI in pulmonary adenocarcinoma.
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PMID:Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastases. 1731 11

Solid evidence for a relationship between lymphangiogenesis and prognosis in human breast cancer is still lacking. Evidence for ongoing lymphangiogenesis in breast cancer is only provided by animal studies. In the present study we investigated lymphatic vessel density as well as the expression level of the lymphangiogenic factors VEGF-C and -D in a series of 121 ductal breast cancer tissues using immunohistochemical stainings. We found that in the primary tumors the lymphatic vessel density, as well as the expression of both VEGF-C and -D, did not relate to grade, tumor stage, progression or patient survival. Furthermore, in tumors in which lymphatic vessels were present, a Ki-67/podoplanin double staining indicated the absence of proliferating lymphatic endothelial cells. In contrast, we did find a correlation between intratumoral lymphatic vessel density inside the lymph node metastases and patient survival. Another parameter that revealed prognostic value was the presence of tumor cells within the lymphatic vessels. This parameter did predict survival in patients with an age below 63 only. Interestingly, expression of VEGF-D was found to be related to the presence of intralymphatic tumor cells.
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PMID:Absence of lymphangiogenesis in ductal breast cancer at the primary tumor site. 1771 60

The expression of NCAM was investigated in tissue sections of 61 cases of papillary carcinoma and in 14 lymph node metastases using immunohistochemistry. Tumour cells of 18 primary tumours were not stained, whereas in the remaining 43 cases, NCAM was expressed in less than 5% tumour cells. Similar results were obtained when NCAM expression was evaluated at the RNA level. Reduced expression of NCAM is an early event since 6/15 cases (40%) of micro-carcinoma were NCAM-negative. NCAM-positive tumour cells were more often located at the invasion front of the tumour. It has been reported that NCAM expression may affect lymphangiogenesis. In tissue sections immunostained for podoplanin, it was found that lymphatic vessels were extremely rare inside the body of the tumour, and were mostly associated with foci of chronic inflammation and/or of reparative fibrosis. Lymphangiogenesis is sustained by VEGF-C, VEGF-D, and FGF2. Analysis of micro-dissected samples of the tumour and of the paired normal thyroid tissue revealed that RNA transcripts for VEGF-D were significantly less numerous in the tumour tissue (p = 0.001). The potential role of NCAM in tumour cell biology was investigated by silencing the NCAM gene in the TPC1 thyroid papillary carcinoma cell line. It was found that NCAM down-regulation caused a significant reduction (p < 0.05) in the expression of both VEGF-C and VEGF-D mRNAs. In addition, NCAM-silenced TPC-1 cells were more adhesive to different extracellular matrix components, and were less efficient in cell migration (59% reduction; p < 0.05) and invasiveness (68% reduction). These latter results confirm that modifications of NCAM expression cause profound alterations in the adhesive and migratory properties of tumour cells, but are in apparent discrepancy with the observation that loss of NCAM is usually associated with increased tumour invasiveness in vivo.
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PMID:Papillary carcinoma of the thyroid: low expression of NCAM (CD56) is associated with downregulation of VEGF-D production by tumour cells. 1757 72

There is controversy regarding whether lymphatic vessels are present or absent in bone. Although lymphangiomas have been described in bone, lymphatic vessels have not been identified morphologically with certainty in any other benign or malignant bone tumors or in normal human bone. In this study, we determined by immunohistochemistry, using 2 specific lymphatic endothelial cell markers, LYVE-1 and podoplanin, whether lymphatics are present in normal bone and a wide range of primary and secondary bone neoplasms. In normal bone, LYVE-1+/podoplanin+ lymphatic vessels were not identified in cortical or cancellous bone but were seen in connective tissue overlying the periosteum. With the exception of lymphangioma, Gorham-Stout disease, and hemangioendothelioma, primary benign and malignant bone tumors (as well as secondary carcinomas) that were confined to bone did not contain lymphatic vessels. Primary and secondary bone tumors that had extended through the bone cortex contained LYVE-1+/podoplanin+ lymphatic vessels that seemed to extend for a short distance from surrounding soft tissues into the tumor. Three cases of osteosarcoma that had extended through the bone cortex and had lymph node metastases were all found to contain lymphatic vessels within the tumor. These results indicate that the lymphatic circulation is unlikely to play a role in bone fluid transport in normal bone and that lymphatic vessels are absent from most primary and secondary tumors confined to bone. These findings also suggest that lymphangiogenesis is not involved in the disease progression of most primary bone tumors and that carcinomatous metastasis to bone does not occur via lymphatics.
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PMID:Lymphatics and bone. 1902 56

Lymphatic invasion by tumor cells has been noted infrequently in primary melanomas. Our primary hypotheses were that using immunohistochemical markers of lymphatic vessels and of tumor cells would improve detection of lymphatic invasion and that lymphatic invasion would correlate with regional nodal metastatic disease. This study included 106 patients who were diagnosed between 1972 and 1991 and who had 10 years or more of follow-up. We performed dual immunohistochemical stains for podoplanin (for lymphatic vessels) and S-100 (for melanoma cells). Lymphatic invasion was identified by light microscopy and confirmed by multispectral imaging analysis. Lymphatic invasion was detected by morphology alone in 5 cases (4.7%) in contrast to immunohistochemical staining augmented by multispectral imaging analysis where 35 cases (33%) were identified (P < .0001). Lymphatic invasion was significantly associated with time to regional nodal metastatic disease, as well as first metastasis and melanoma-specific death. "Local metastasis," defined by immunohistochemistry-detected lymphatic invasion, satellites, or neural invasion, identified 64% of those who had regional nodal metastatic disease within 5 years of diagnosis. Lymphatic invasion is an underobserved phenomenon in primary melanomas that can be better detected by immunohistochemical staining. The presence of lymphatic invasion may be a clinically useful predictor of regionally metastatic disease.
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PMID:Lymphatic invasion revealed by multispectral imaging is common in primary melanomas and associates with prognosis. 1844 May 91

Metastasis is the major cause of death from cancer, yet the optimal strategy against it remains uncertain. The pathogenesis of hematogenous metastasis is dynamic and consists of the following steps: 1) detachment of tumor cells from the primary site, 2) invasion into the host's blood vessels, 3) migration in the host's blood stream, 4) transport along the circulation, 5) arrest in or adhesion to the capillary in a distant organ, 6) extravasation, and 7) proliferation within the foreign tissues. A key to successful hematogenous metastasis is tumor survival in the bloodstream because most circulating tumor cells are rapidly destroyed by the shear forces or are attacked by the immune system. Less than 0.01% of these cells result in metastasis. Tumor cell-induced platelet aggregation has been reported to facilitate hematogenous metastasis by increasing the arrest of tumor cell emboli in the microcirculation. Platelet aggregation is also believed to protect tumor cells from immunological assault in the circulation. We have identified Aggrus as a platelet-aggregating factor expressed on a number of human cancers. Because hematogenous metastasis is reduced when neutralizing antibodies or eliminating carbohydrates attenuates Aggrus function, Aggrus's main contribution to hematogenous metastasis of Aggrus-expressing cells, then, is by promoting platelet aggregation. Aggrus could serve as an ideal target for drug development to block metastasis.
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PMID:Platelet aggregation in the formation of tumor metastasis. 1894 Dec 98

Lung cancer represents one of the most frequent causes of death due to neoplastic disease in Poland and around the world. The high mortality which accompany neoplastic diseases used to be ascribed mainly to dissemination of cancerous cells. Studies on animal models suggest that tumour lymphangiogenesis represents the principal factor in the process of metastases formation. Lymphangiogenesis involves a process of formation of new lymphatic vessels from already existing lymphatic capillaries. Lymphangiogenesis is stimulated by vascular endothelial growth factors (VEGF) and other, recently reported factors, such as, e.g., cyclooxygenase 2, fibroblast growth factor 2, angiopoetin-1 and the insulin-resembling growth factor. In lymphangiogenesis a key role is played by neutropilin 2 or podoplanin and this promoted development of studies on lymphangiogenesis. Activation of VEGF-C/VEGF-D/VEGFR-3 axis increases motility and invasiveness of neoplastic cells, promotes development of metastases in several types of tumours such as, e.g., lung cancer, mammary carcinoma, cancers of the neck, prostate and large intestine. In recent years lymphangiogenesis provided topic of many studies. A positive correlation was detected between expressions of VEGF-C/D and VEGFR-3 in non-small cell lung cancer. In patients with lung cancer with high expression of VEGF-C a markedly abbreviated survival was noted. Positive correlation was detected between expression of VEGF-C and VEGF-D on one hand and expression of LYVE-1 on the other in sentinel lymph nodes with metastases of neoplastic cells in patients with non-small cell lung cancer. Also, high density of lymphatic vessels and high density of intraneoplastic microvessels proved to be independent poor prognostic indices in patients with non-small cell lung cancer. Extensive hope is linked to studies on inhibitors of lymphangiogenesis, which may improve results of treatment also in tumour patients.
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PMID:Role of lymphangiogenesis in lung cancer. 2016 15


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