Immunohistochemical demonstration of proliferating lymphatic vessels in colorectal carcinoma and its clinicopathological significance

ArticleinCancer Letters 246(1-2):167-72 · March 2007with10 Reads
DOI: 10.1016/j.canlet.2006.02.013 · Source: PubMed
Lymphatic metastasis to the regional lymph nodes through the lymphatic vessels is an important indicator of poor prognosis in many types of malignant tumors. Recently, much attention has been paid to lymphangiogenesis for its possible role on tumor progression in various carcinomas. However, morphological evidence that lymphatic vessels actively proliferate in colorectal carcinoma has not been reported. Here, we first devised a triple immunostaining method to detect proliferating lymphatic vessels utilizing antibody to Ki-67 antigen as a marker of cell proliferation, antibody to cytokeratin as an epithelial cell marker, and antibody to podoplanin as a lymphatic vessel-specific marker. Ki-67/podoplanin-immunoreactivity enabled us to identify proliferating lymphatic vessels, while cytokeratin immunoreactivity allowed us to distinguish proliferating lymphatic vessels from Ki-67/cytokeratin-positive carcinoma cells in lymphatic lumens. Analyzing 64 colorectal carcinoma patients' samples using this technique, we showed that both lymphatic vessel density and proliferating activity of lymphatic vessels were significantly increased in colorectal carcinoma tissues compared with their normal counterparts. We then examined the correlation between the degree of lymphangiogenesis and patients' prognosis or clinicopathological variables, but no statistically significant differences were obtained in these analyses. Thus, these results combined together indicate that extensive lymphangiogenesis occurs in colorectal carcinoma, but that the degree of lymphangiogenesis alone is not an independent prognostic factor for this disease.
    • "3. MKI67 expression is a reliable marker for predicting metastatic potential of rectal carcinoid (Hotta et al., 2006). 4. The expression of MKI67, PDPN (podoplanin) and cytokeratin are correlated with increased lympangiogenesis but not with poorer prognosis (Omachi et al., 2007). 5. Decreased expression of MKI67, HIF1A and BCL2 markers were found after chemoradiotherapy of rectal cancer (Havelund et al., 2013). "
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    • "In solid human tumors the clinicopathological significance of VEGF-C/VEGF-D status currently remains controversial (Table 2). For CRC a significantly higher expression level of VEGF-C/VEGFR-3 compared to normal tissue is described [21].Figure 4 shows a histopathological result of VEGF-C expression. The majority of studies (such as esophageal, gastric, pancreatic or colorectal) have found a positive correlation between overexpression of VEGF-C/VEGF-D on the one hand and vascular invasion, lymph vessel and lymph node involvement , distant metastasis and poor clinical outcome on the other hand222324252627. "
    [Show abstract] [Hide abstract] ABSTRACT: Tumor cell dissemination from the primary tumor site to distant organs is one of the characteristic properties of malignant tumors and represents a crucial step in the progression of disease. Although the pattern of spread may vary in different types of carcinomas, dissemination via the lymphatic system represents a common event in metastasis. The extent of lymph node metastasis is one of the major determinants for the prognosis of patients with gastrointestinal carcinomas and guides the therapeutically management. During the last decades, significant attention has been given to the molecular mechanisms that control lymphatic metastasis. The process of lymphangiogenesis has come into the focus. Lymphangiogenesis, the formation of newly lymphatics, comprises a series of complex cellular events and is controlled by a balance between pro- and anti-lymphangiogenic signals. This article will briefly describe the lymphatic system and then provide an overview of the molecular players involved in tumor lymphangiogenesis.
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    • "The study of lymphatics has been facilitated by the identification of the lymphatic marker LYVE-11314151617. LYVE-1 is found in lymphatic endothelium and not in blood vascular endothelium except in the sinusoidal endothelium of liver and spleen where uptake and degradation of HA is known to occur [17]. There is controversy regarding lymphatics and lymphangiogenesis in the endometrium. "
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