Expression of PROX-1 in oral Kaposi's sarcoma spindle cells.

BACKGROUND: The histogenesis of neoplastic spindle cells of Kaposi's sarcoma is still uncertain, but some studies consider it a lymphatic vessel differentiation. Prox-1 is a nuclear transcription factor that plays a major role during embryonic lymphangiogenesis, and it has been considered a specific and sensitive lymphatic endothelial cell marker. The aim of this study was to determine the expression of Prox-1 in oral Kaposi's sarcoma comparing the results with oral benign vascular tumors including capillary hemangiomas and pyogenic granulomas. METHODS: Expression of Prox-1 and HHV-8 was evaluated by immunohistochemistry in 30 oral Kaposi's sarcoma, 5 oral capillary hemangiomas, and 10 oral pyogenic granulomas. The labeling index was expressed as the percentage of positive cells for each case studied. Statistical comparison was performed using the Wilcoxon-Mann-Whitney rank sum test. RESULTS: Twenty-eight (93.3%) and 30 oral Kaposi's sarcoma cases were positive for Prox-1 and HHV-8, respectively, while all oral benign vascular tumors were negative for these markers. The number of Prox-1 and HHV-8 oral Kaposi's sarcoma-positive cells increased significantly from patch/plaque to nodular histological stages. CONCLUSION: The expression of Prox-1 in the neoplastic spindle cells supports the view of a lymphatic differentiation in oral Kaposi's sarcoma. Prox-1 may also be involved in the pathogenesis of oral Kaposi's sarcoma as the number of positive spindle cells increased progressively from patch to nodular stages and could be eventually useful as an additional diagnostic tool for differential diagnosis between oral Kaposi's sarcoma and benign oral vascular lesions.

Role of high endothelial postcapillary venules and selected adhesion molecules in periodontal diseases: a review.

Periodontitis is accompanied by the proliferation of small blood vessels in the gingival lamina propria. Specialized postcapillary venules, termed periodontal high endothelial-like venules, are also present, and demonstrate morphological and functional traits similar to those of high endothelial venules (HEVs) in lymphatic organs. The suggested role of HEVs in the pathogenesis of chronic periodontitis involves participation in leukocyte transendothelial migration and therefore proinflammatory effects appear. Recent observations suggest that chronic periodontitis is an independent risk factor for systemic vascular disease and may result in stimulation of the synthesis of acute phase protein by cytokines released by periodontal high endothelial cells (HECs). However, tissue expression of HEV-linked adhesion molecules has not been evaluated in the gingiva of patients with chronic periodontitis. This is significant in relation to potential therapy targeting expression of the adhesion molecules. In this review, current knowledge of HEV structure and the related expression of four surface adhesion molecules of HECs [CD34, platelet endothelial cell adhesion molecule 1, endoglin and intercellular adhesion molecule 1 (ICAM-1)], involved in the key steps of the adhesion cascade in periodontal diseases, are discussed. Most studies on the expression of adhesion molecules in the development and progression of periodontal diseases pertain to ICAM-1 (CD54). Studies by the authors demonstrated quantitatively similar expression of three of four selected surface markers in gingival HEVs of patients with chronic periodontitis and in HEVs of reactive lymph nodes, confirming morphological and functional similarity of HEVs in pathologically altered tissues with those in lymphoid tissues.

Absence of lymphatic vessels in the dog dental pulp: an immunohistochemical study.

In spite of numerous investigations it has not been precisely determined whether lymphatic vessels are present in the dental pulp of dogs. Therefore, this study attempted a specific immunohistochemical detection of lymphatic endothelium. The canine teeth of 19 healthy beagle dogs were dissected into three segments (apical, intermediate and occlusal). After decalcification, specimens were embedded in paraffin wax and histologic cross-sections were stained immunohistochemically using a reliable antibody (anti-Prox-1) against the homeobox transcription factor Prox-1, which is located within the nucleus of lymphatic endothelium. Anti-Prox-1 reacted positively with canine control tissues (lymph nodes, gingiva, nasal mucosa), but showed no staining in tissue sections of the dental pulp. The dog dental pulp contained no vascular structures lined with lymphatic endothelium. This suggests that drainage of interstitial fluid makes use of other routes, i.e. extravascular pathways.

Specialized postcapillary venules in human gingival tissue.

High endothelial venules (HEV) are specialized postcapillary venules that play a central role in lymphocyte migration and recirculation. This study examined the occurrence and morphology of HEV-like vessels in healthy gingiva and in lesions of chronic gingivitis in children, experimental gingivitis in adults, adult periodontitis, and in periapical granulomas. HEV-like vessels were absent in gingival health, but present during the development of inflammation and in chronic inflammation. The morphology of these HEV-like vessels in the oral cavity resembled that of lymphoid HEV. Thus gingival HEV may represent sites for the entry of lymphocytes into chronic inflammatory lesions.

Expression of cys-cys chemokine ligand 21 on human gingival lymphatic vessels.

The cys-cys (C-C) chemokine ligand 21 is a member of the C-C chemokines that constitute a group of heparin-binding cytokines with a pattern of four or six conserved cysteines. The CCL21 is known to be expressed in secondary lymphoid tissues, however it has rarely been reported for the expression on peripheral lymphatic vessels in somatic tissue. Here we investigated the expression of CCL21 on lymphatic vessels identified by anti-desmoplakin in uninflamed and inflamed human gingiva. In uninflamed tissue the expression of CCL21 was detected on lymphatic vessels in gingiva. In uninflamed gingiva the expression of CCL21 was detected on all lymphatic capillaries of the mucosal connective tissue papillae. There were two types of collecting lymphatic vessels in the lamina propria mucosae expressing CCL21 strongly or very weakly. In inflamed gingiva no expression of CCL21 was detected on lymphatic vessels. In all tissue sections no blood vessels expressing CCL21 were observed. These results may suggest that the expression of CCL21 is predominantly induced in the peripheral lymphatic endothelium of the uninflamed mucosal microcirculation, and that under inflamed conditions a reduction of CCL21 occurs in lymphatic endothelium.

Weibel-Palade bodies and lymphatic endothelium: observations in the lymphatic vessels of normal and inflamed human dental pulps.

The Weibel-Palade bodies, cytoplasmic organelles characterizing endothelial cells, are abundant in lymphatic capillary endothelium of human dental pulp. Their number almost double in the lymphatic vessels of inflamed dental pulps. The data were discussed and compared with others concerning the demonstration of the presence of von Willebrand factor and P-selectin in the Weibel-Palade bodies of lymphatic vessels in mesentery. It is suggested that the increase in the number of Weibel-Palade bodies observed in dental pulp may be connected along with those in the lymphatic vessels to the function that these adhesive molecules play during inflammatory states.

Expression of junctional adhesion molecules on the human lymphatic endothelium.

Human lymphatic vessels express several leukocyte adhesion molecules. The study here investigated the expression of three junctional adhesion molecules (JAM) which are a newly reported glycoprotein family of adhesion molecules on human lymphatic endothelium. In this study, JAM-1 and JAM-3 but not JAM-2 were detected in cultured human neonatal dermal lymphatic endothelial cells (LEC) at the gene and protein levels by microarray, RT-PCR, real-time PCR, and immunohistochemical analysis. The JAM-1 and JAM-3 expression was not altered in the TNF-alpha-treated LEC or in the untreated cells. In human tissue, the expression of JAM-1, and the expression of JAM-1, JAM-2, and JAM-3 were observed in collecting lymphatic vessels of uninflamed small intestine, and in initial lymphatics of inflamed tongue and uninflamed gingival tissue. It is thought that JAM-2 mRNA could be produced in mature vascular endothelium but not in cultured cells, and that human intestinal and oral lymphatic vessels usually express JAM-1, JAM-2, and JAM-3. There were initial lymphatics simultaneously expressing JAM-1, JAM-2, and JAM-3 in the mucosal connective tissue papillae of gingival tissue. The three JAM expressions on the lymphatic endothelium may contribute to both seal the cell-cell contact at interendothelial junctions and also allow lymphocytes to transmigrate into lymphatic vessels from tissue, independent of inflammatory cytokines.

Lymphocyte entry into inflammatory tissues in vivo. Qualitative differences of high endothelial venule-like vessels in sponge matrix allografts vs isografts.

Sponge matrix allografts and isografts become extensively encapsulated and neovascularized after s.c. implantation. Sponge allografts acquire alloantigen-reactive T lymphocytes, whereas sponge isografts fail to do so, even though these T cells are continuously circulating in the peripheral blood. We have investigated the possibility that the vascular endothelia regulates lymphocytic accumulation in sponge matrix implants. In normal lymph nodes, specialized high endothelial venules (HEV) regulate lymphocyte extravasation from the blood. We have now identified HEV-like vessels in sponge matrix allografts. These vessels are operationally defined as "HEV-like" in that they react with mAb MECA 325 which identifies murine HEV, and bind lymphocytes in ex vivo adhesion assays. In contrast, sponge isografts contain MECA 325 reactive vessels that are significantly smaller than those found in allografts. Further, vessels of sponge isografts do not readily bind lymphocytes in ex vivo adhesion assays. Immunohistologic analysis also revealed that the small MECA 325+ vessels present in sponge isografts are consistently found in close proximity to nerve bundles. Although this MECA 325 reactive vessel-nerve bundle association is also observed in sponge allografts, large MECA 325 reactive vessels are widely distributed in allografts. Our data suggest that small, poorly adhesive MECA 325 reactive vessels develop in sponge isografts and allografts, possibly under the influence of local nerve tissue. These vessels respond to regional alloimmune responses by developing into the larger HEV-like vessels capable of binding lymphocytes in sponge allografts. The value of this experimental system as an in vivo model to evaluate mechanisms involved in neovascularization and endothelial differentiation is discussed.