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World Journal of Surgical Oncology

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Open Access 01-12-2017 | Research

Correlation between lymphatic endothelial markers and lymph node status or N-staging of colorectal cancer

Authors: Xing-mao Zhang, Wen-xiao Han, Hong-ying Wang, Qiang He

Published in: World Journal of Surgical Oncology | Issue 1/2017

Abstract

Background

The purpose of this study is to examine the expression levels of lymphatic endothelial markers in colorectal cancer and to explore the correlation between the expression levels of markers and lymph node status.

Methods

Forty-seven paired fresh tumor tissues and para-cancerous tissues were collected from colorectal cancer patients who received surgical treatment between August 2015 and March 2016 in Cancer Hospital, Chinese Academy of Medical Sciences. Real-time quantitative PCR (RTQ–PCR) was used to check the expression levels of LYVE–1, VEGFR–3, Podoplanin, and Prox–1 in tumor and para-cancerous tissues.

Results

The positive expression rates of LYVE–1, VEGFR–3, Podoplanin, and Prox–1 in tumor tissues were 100, 93.6, 100, and 91.4%, but 100, 100, 100, and 87.2% in para-cancerous tissues. Comparing with para-cancerous tissues, tumor tissues had significantly lower expression levels of LYVE–1 (P < 0.001) and VEGFR–3 (P = 0.013) and higher levels of Podoplanin (P = 0.016) and Prox–1 (P = 0.078). There was no correlation between lymph node status and the expression level of LYVE–1 in tumor tissues (P = 0.354) or par-cancerous tissues (P = 0.617); similar results were found for VEGFR–3 (P = 0.631, 0.738), Podoplanin (P = 0.490, 0.625), and Prox–1 (P = 0.503, 0.174). Meanwhile, there was no correlation between N-staging and the expression level of LYVE–1 in tumor tissues (P = 0.914) or para-cancerous tissues (P = 0.784); similar results were found for VEGFR–3 (P = 0.493, 0.955), Podoplanin (P = 0.199, 0.370), and Prox–1 (P = 0.780, 0.234).

Conclusions

There was no correlation between expression levels of lymphatic endothelial markers and lymph node status; LYVE–1, VEGFR–3, Podoplanin, and Prox–1 could not be used for predicting the lymph node status or N-staging of colorectal cancer.

Sundar SS, Zhang H, Brown P, Manek S, Han C, Kaur K, et al. Role of lymphangiogenesis in epithelial ovarian cancer. Br J Cancer. 2006;94:1650–7.CrossRefPubMedPubMedCentral

Sundar SS, Ganesan TS. Role of lymphangiogenesis in cancer. J Clin Oncol. 2007;25:4298–307.CrossRefPubMed

Hall FT, Freeman JL, Asa SL, Jackson DG, Beasley NJ. Intratumoral lymphatics and lymph node metastases in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 2003;129:716–9.CrossRefPubMed

Beasley NJ, Prevo R, Banerji S, Leek RD, Moore J, van Trappen P, et al. Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer. Cancer Res. 2002;62:1315–20.PubMed

Kawakami M, Furuhata T, Kimura Y, Yamaguchi K, Hata F, Sasaki K, et al. Quantification of vascular endothelial growth factor-C and its receptor-3 messenger RNA with real-time quantitative polymerase chain reaction as a predictor of lymph node metastasis in human colorectal cancer. Surgery. 2003;133:300–8.CrossRefPubMed

Yamanashi T, Nakanishi Y, Fujii G, Akishima-Fukasawa Y, Moriya Y, Kanai Y, et al. Podoplanin expression identified in stromal fibroblasts as a favorable prognostic marker in patients with colorectal carcinoma. Oncology. 2009;77:53–62.CrossRefPubMed

Agarwal B, Saxena R, Morimiya A, Mehrotra S, Badve S. Lymphangiogenesis does not occur in breast cancer. Am J Surg Pathol. 2005;29:1449–55.CrossRefPubMed

Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, et al. LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol. 1999;144:789–801.CrossRefPubMedPubMedCentral

Schledzewski K, Falkowski M, Moldenhauer G, Metharom P, Kzhyshkowska J, Ganss R, et al. Lymphatic endothelium-specific hyaluronan receptor LYVE-1 is expressed by stabilin-1+, F4/80+, CD11b+ macrophages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro: implications for the assessment of lymphangiogenesis. J Pathol. 2006;209:67–77.CrossRefPubMed

10.

Wu M, Du Y, Liu Y, He Y, Yang C, Wang W, et al. Low molecular weight hyaluronan induces lymphangiogenesis through LYVE-1-mediated signaling pathways. PLoS One. 2014;9:e92857.CrossRefPubMedPubMedCentral

11.

Cunnick GH, Jiang WG, Gomez KF, Mansel RE. Lymphangiogenesis quantification using quantitative PCR and breast cancer as a model. Biochem Biophys Res Commun. 2001;288:1043–6.CrossRefPubMed

12.

Ozmen F, Ozmen MM, Ozdemir E, Moran M, Seckin S, Guc D, et al. Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer. World J Gastroenterol. 2011;17:3220–8.PubMedPubMedCentral

13.

Gao F, Lu YM, Cao ML, Liu YW, He YQ, Wang Y. Expression and quantification of LYVE-1 in human colorectal cancer. Clin Exp Med. 2006;6:65–71.CrossRefPubMed

14.

Lu Y, Yang Q, Du Y, Feng G, Yang C. Expression analysis of lymphangiogenic factors in human colorectal cancer with quantitative RT-PCR. Cancer Investig. 2007;25:393–6.CrossRef

15.

Pajusola K, Aprelikova O, Korhonen J, Kaipainen A, Pertovaara L, Alitalo R, et al. FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines. Cancer Res. 1992;52:5738–43.PubMed

16.

Galland F, Karamysheva A, Pebusque MJ, Borg JP, Rottapel R, Dubreuil P, et al. The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor. Oncogene. 1993;8:1233–40.PubMed

17.

Okita NT, Yamada Y, Takahari D, Hirashima Y, Matsubara J, Kato K, et al. Vascular endothelial growth factor receptor expression as a prognostic marker for survival in colorectal cancer. Jpn J Clin Oncol. 2009;39:595–600.CrossRefPubMed

18.

Smith NR, Baker D, James NH, Ratcliffe K, Jenkins M, Ashton SE, et al. Vascular endothelial growth factor receptors VEGFR-2 and VEGFR-3 are localized primarily to the vasculature in human primary solid cancers. Clin Cancer Res. 2010;16:3548–61.CrossRefPubMed

19.

Roy S, Chu A, Trojanowski JQ, Zhang PJ. D2-40, a novel monoclonal antibody against the M2A antigen as a marker to distinguish hemangioblastomas from renal cell carcinomas. Acta Neuropathol. 2005;109:497–502.CrossRefPubMed

20.

Braun M, Flucke U, Debald M, Walgenbach-Bruenagel G, Walgenbach KJ, Holler T, et al. Detection of lymphovascular invasion in early breast cancer by D2-40 (podoplanin): a clinically useful predictor for axillary lymph node metastases. Breast Cancer Res Treat. 2008;112:503–11.CrossRefPubMed

21.

Wada H, Shiozawa M, Katayama K, Okamoto N, Miyagi Y, Rino Y, et al. Systematic review and meta-analysis of histopathological predictive factors for lymph node metastasis in T1 colorectal cancer. J Gastroenterol. 2015;50:727–34.

22.

Wigle JT, Harvey N, Detmar M, Lagutina I, Grosveld G, Gunn MD, et al. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J. 2002;21:1505–13.CrossRefPubMedPubMedCentral

23.

Parr C, Jiang WG. Quantitative analysis of lymphangiogenic markers in human colorectal cancer. Int J Oncol. 2003;23:533–9.PubMed

Title: Correlation between lymphatic endothelial markers and lymph node status or N-staging of colorectal cancer
Authors: Xing-mao Zhang
Wen-xiao Han
Hong-ying Wang
Qiang He
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2017
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/s12957-017-1276-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Correlation between lymphatic endothelial markers and lymph node status or N-staging of colorectal cancer

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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