Increased density and diameter of lymphatic microvessels correlate with lymph node metastasis in early stage invasive colorectal carcinoma

Liang, Pan; Hong, Jian-Wei; Ubukata, Hideyuki; Liu, Huanran; Watanabe, Yoshinori; Katano, Motonobu; Motohashi, Gyo; Kasuga, Teruhiko; Nakada, Ichiro; Tabuchi, Takafumi

doi:10.1007/s00428-006-0166-9

Cited by 61 publications

(56 citation statements)

References 20 publications

(28 reference statements)

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“…In a VEGF-C overexpressing animal model, a tumour-induced increase in the diameter of collecting lymphatic vessels was associated with an enhanced passage of clusters of tumour cells to the sentinel LNs (He et al, 2005). Increased lymphatic vessel perimeters and areas were also found to be correlated with the occurrence of lymphatic metastasis in some human tumours (Nathanson et al, 1997;Dadras et al, 2003;Franchi et al, 2004;Liang et al, 2006;Massi et al, 2006).…”

Section: Lymphatic Endothelial Cell Proliferation (Lecp)mentioning

confidence: 99%

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

et al. 2006

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The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra-and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment. Metastasis is the leading cause of cancer mortality. Metastatic cancer cells can escape from their site of origin and spread to distant organs through invasion of the vascular system and/or the lymphatic system. Tumour vascularisation is widely accepted as a bona fide indicator of tumour growth, metastases and patient survival. In 1996, Peter Vermeulen et al (1996) published a first international consensus on the methodology and criteria of the evaluation of angiogenesis quantification in solid tumours and 5 years later, a second consensus report, in which new concepts and mechanisms of tumour vascularisation were integrated, appeared (Vermeulen et al, 2002). Both reports were aimed at improving the standardisation of angiogenesis quantification in order to allow intratumourous microvessel density to be applied as a prognostic indicator and, moreover, as a reliable predictor of the risk of malignant transformation of premalignant lesions and of response to cancer treatment. Contrary to angiogenesis, the de novo formation of lymphatic vessels or lymphangiogenesis and its role in promoting the metastatic spread of tumour cells has only recently become a focal point of cancer research with an increasing number of studies showing a relationship between patient survival and lymphatic density in different tumour types. In order to confirm the potential prognostic value of lymphangiogenesis in patients with cancer, a quantification method that is characterised by a low intra-and interobserver variability needs to be developed. In this first consensus report, we would like to provide an overview of current concepts of the lymphatic vasculature and its regulating factors and propose guidelines for the estimation of the ongoing lymphangiogenesis in solid human tumour sections.

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Section: Lymphatic Endothelial Cell Proliferation (Lecp)mentioning

confidence: 99%

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

et al. 2006

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“…3,4 They have been suggested to produce pro-invasive signals that induce a more aggressive phenotype in the tumor. 5,6 CAFs are not transformed genetically, but differ from resting fibroblasts with regard to morphology, gene expression, and the production of important biological mediators, such as growth factors and proteases. 7 They are often referred to as activated fibroblasts and have been seen to express the protease fibroblast activation protein (FAP)-␣.…”

mentioning

confidence: 99%

Colorectal Cancer Cells Activate Adjacent Fibroblasts Resulting in FGF1/FGFR3 Signaling and Increased Invasion

Henriksson

Edin

Dahlin

et al. 2011

The American Journal of Pathology

118

100

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Cancer-associated fibroblasts expressing fibroblast activation protein (FAP) have been implicated in the invasive behavior of colorectal cancer. In this study, we use FAP expression as a marker of fibroblast activation and analyze the effect of activated fibroblasts on colorectal cancer migration and invasion in experimental cell studies. We also investigated the expression pattern of FAP in cancer-associated fibroblasts during transformation from benign to malignant colorectal tumors. In immunohistochemical analyses, FAP was expressed in fibroblasts in all colorectal cancer samples examined, whereas all normal colon, hyperplastic polyps, or adenoma samples were negative. In in vitro studies, conditioned medium from colon cancer cells, but not adenoma cells, activated fibroblasts by inducing FAP expression. These activated fibroblasts increased the migration and invasion of colon cancer cells in Boyden chamber experiments and in a three-dimensional cell culture model. We identify fibroblast growth factor 1/fibroblast growth factor receptor 3 (FGF1/FGFR-3) signaling as mediators leading to the increased migration and invasion. Activated fibroblasts increase their expression of FGF1, and by adding a fibroblast growth factor receptor inhibitor, as well as an FGF1-neutralizing antibody, we reduced the migration of colon cancer cells. Our findings provide evidence of a possible molecular mechanism involved in the cross talk between cancer cells and fibroblasts leading to cancer cell invasion.

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“…Possible risk factors for lymph node metastasis in submucosal invasive colorectal carcinoma include the depth of submucosal invasion, poorly differentiated histology, lymphatic vessel invasion, expression of vascular endothelial growth factor-A and -C, and expression of β-catenin (Takayama et al 1998;Maeda et al 2003;Kojima et al 2005;Walgenbach-Bruenagel et al 2006;Liang et al 2006;Saad et al 2006;Kaneko et al 2007a;Ishii et al 2009). Several studies have reported that tumor budding is a histological risk factor for lymph node metastasis of colorectal carcinoma (Hori et al 2005;Park et al 2005;Masaki et al 2006;Kaneko et al 2007b).…”

mentioning

confidence: 99%

Prognostic and Diagnostic Significance of Tumor Budding Associated with β-Catenin Expression in Submucosal Invasive Colorectal Carcinoma

Umemura

Takagi

Shimada

et al. 2013

Tohoku J. Exp. Med.

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Endoscopic resection has become a major curative treatment for early colorectal carcinoma without lymph node metastasis. However, lymph node metastasis, a poor prognostic factor in colorectal carcinoma, occurs in about 10% of the patients with submucosal invasive colorectal carcinoma. Therefore, it is important to identify a high-risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma. This study was designed to identify the relationship between tumor budding with β-catenin expression and lymph node metastasis in submucosal invasive colorectal carcinoma. We investigated the immunohistochemistry of tumor budding in the 142 patients who underwent surgical resection for submucosal invasive colorectal carcinomas between 1984 and 1999 and the expression pattern of β-catenin in budding tumor cells. Accordingly, all the patients were followed up for at least 10 years or until death. Among the 142 patients, lymph node metastasis was detected in 14 patients (9.9%). Univariate analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was significantly associated with lymph node metastasis (P = 0.005). In contrast, tumor budding detected by hematoxylin and eosin staining was not associated with lymph node metastasis. Multivariate logistic regression analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was a significant risk factor for lymph node metastasis (odds ratio, 7.124; 95% confidence interval, 1.407-36.062). Thus, tumor budding associated with β-catenin expression is a risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma.

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Increased density and diameter of lymphatic microvessels correlate with lymph node metastasis in early stage invasive colorectal carcinoma

Cited by 61 publications

References 20 publications

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

Colorectal Cancer Cells Activate Adjacent Fibroblasts Resulting in FGF1/FGFR3 Signaling and Increased Invasion

Prognostic and Diagnostic Significance of Tumor Budding Associated with β-Catenin Expression in Submucosal Invasive Colorectal Carcinoma

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