OJPathology  Vol.4 No.3 , July 2014
Cancer-Associated Lymphatic and Venous Vessels in Colonic Carcinomas
Abstract: Objective: Colonic carcinomas spread to regional lymph nodes and liver. There are cancer-associated lymphatic and venous vessels at the margin of colonic carcinomas, which facilitate spreading carcinoma through lymphatic and venous vessels. This study aimed to examine cancer-associated lymphatic and venous vessels in TNM T1 to T3 carcinomas using lymphatic vessel hyaluronan receptor for lymphatic vessels and von Willebrand factor for venous vessels by immunocytochemical staining. Materials and Methods: A total of 40 cases of moderately differentiated colonic carcinoma were studied using routinely formalin-fixed and paraffin-embedded sections. The cases consisted of 10 cases of TNM T1, 15 cases each of T2 and T3 cases. Immunocytochemical staining was performed using goat antihuman LYVE-1for lymphatic vessels and rabbit antihuman von Willebrand factor for venous vessels. Results: In TNM T1 carcinoma, increased, irregular and narrow lymphatic and venous vessels were present in the adjacent normal mucosa to the carcinoma, some of which penetrated cancerous lesion. There were no tumor emboli in lymphatic and venous vessels. In TNM T2 carcinoma, there were few lymphatic and venous vessels in midst of the carcinoma whereas numerous small lymphatic and venous vessels were present within muscle layers adjacent to the invading carcinoma. Extramural tumor embolus was present in submucosa in one case. In TNM T3 carcinoma, cancer has invaded through the muscle layers where dilated lymphatic and venous vessels were present adjacent to cancerous nests. Tumor emboli were identified in two cases by immunocytochemical staining. Conclusion: The current study showed cancer-associated lymphatic and venous vessels at the interface in TNM T1 carcinoma to dilated intramuscular lymphatic and venous vessels adjacent to invading cancerous nests in TNM T3 carcinoma, and supports cancerous cells spread via lymphatic and venous vessels through muscle layers to subserosa as supported by tumor emboli in the lymphovascular system.
Cite this paper: Tomita, T. (2014) Cancer-Associated Lymphatic and Venous Vessels in Colonic Carcinomas. Open Journal of Pathology, 4, 101-109. doi: 10.4236/ojpathology.2014.43016.

[1]   Rosai, J. (2004) Large Bowel, Carcinoma. In: Rosai, J., Ed., Rosai and Ackerman’s Surgical Pathology, 9th Edition, Mosby, St. Louis, 810-825.

[2]   Shida, H., Ban, H, Matsumoto, M., Masuda, K., et al. (1992) Prognostic Significance of Location of Lymph Node Metastasis in Colorectal Cancer. Diseases of Colon and Rectum, 32, 1046-1050.

[3]   Morodomi, T., Isomoto, H., Shirouzu, K., Kageyama K., et al. (1989) An Index for Estimating the Probability of Lymph Node Metastasis in Rectal Carcinoma. Cancer, 63, 539-543.<539::AID-CNCR2820630323>3.0.CO;2-S

[4]   Futamura, M., Takagi, Y., Koumura, H., Kida H., et al. (1998) Spread of Colorectal Cancer Micrometastasis in Regional Lymph Node by Reverse Transcriptase-Polymerase Chain Reaction for Carcinoembryonic Antigen and Cytokeratin 20. Journal of Surgical Oncology, 68, 34-40.<34::AID-JSO8>3.0.CO;2-M

[5]   Andreola, S., Leo, E., Belli, F., Gallino, G., et al. (2001) Adenocarcinoma of the Lower Third of the Rectum: Metastasis in Preliminary Result on Early Tumor Recurrence. Annul of Surgical Oncology, 8, 413-417.

[6]   Wang, H.S., Liang, W.Y., Lin, T.C., et al. (2005) Curative Resection of T1 Colorectal Carcinoma: Risk of Lymph Node Metastasis and Long-Term Prognosis. Diseases of the Colon and Rectum, 48, 1182-1192.

[7]   Ishii, M., Ota, M., Saito, S., Kinugasa, Y., et al. (2009) Lymphatic Vessel Invasion Detected by Monoclonal Antibody D2-40 as a Predictor of Lymph Node Metastasis in T1 Colorectal Cancer. International Journal of Colorectal Disease, 24, 1069-1074.

[8]   Imada, K., Shimokawa, K., Ikeda, T., Hayashi, M., et al. (1991) Development of Liver Metastasis in Colorectal Carcinoma. With Special Reference to Venous Invasion and Basement Membrane Laminin. Acta Pathologica Japonica, 41, 2240-2245.

[9]   Fong, Y. and Blumgart, L.H. (1998) Hepatic Colorectal Metastasis: Current Status of Surgical Therapy. Oncology, 12, 1489-1498.

[10]   Stacker, S.A., Achen, M.G., Jussila, L., Baldwin, M.E. and Alitalo, K. (2002) Lymphangiogenesis and Cancer Metastasis. Nature Rev Cancer, 2, 573-583.

[11]   He, Y., Rajantie, I., Ilmonen, M., Makinen, T., et al. (2004) Preexisting Lymphatic Endothelium But Not Endothelial Progenitor Cells Are Essential for Tumor Lymphangiogegnesis and Lymphatic Metastasis. Cancer Research, 64, 3737-3740.

[12]   Sharinen, P., Tammela, T., Karkkanen, M.J. and Alitalo, K. (2004) Lymphatic Vasculature: Development, Molecular Regulation and Role in Tumor Metastasis and Inflammation. Trends in Immunology, 25, 387-395.

[13]   Tomita, T. (2008) Immunocytochemical Localization of Lymphatic and Venous Vessels in Colonic Polyps and Adenomas. Digestive Diseases and Science, 53, 1880-1885.

[14]   Quirke, P. and Morris, E. (2007) Reporting Colorectal Carcinoma. Histopathology, 50, 103-112.

[15]   Zimmerman, R.L., Ross, H.M. and Gausa, R.E. (2004) Identification of Lymphatic Vessels in Malignant, Adenomatous and Normal Colonic Mucosa Using the Novel Immunostain D2-40. Oncology Report, 11, 47-50.

[16]   Zanetta, L., Marcus, S.G., Vasile, J., Dobryansky, M., Cohen, H., et al. (2000) Expression of von Willebrand Factor, an Endothelial Cell Marker, Is Up-Regulated by Angiogenesis Factors: A Potential Method for Objective Assessment of Tumor Angiogenesis. International Journal of Cancer, 85, 281-288.;2-3

[17]   Fiedler, U., Christian, S., Koidl, S., Kerjaschki, D. and Emmett, M.S. (2006) The Sialomucin CD 34 Is a Marker of Lymphatic Endothelial Cells in Human Tumors. American Journal of Pathology, 168, 1045-1053.

[18]   Matsumoto, K., Nakayama, Y., Inoue, Y., Minagawa, N., et al. (2007) Lymphatic Microvessels Density Is an Independent Prognostic Factor in Colorectal Carcinoma. Diseases of the Colon and Rectum, 50, 308-314.

[19]   Kaneko, I., Tanaka, S., Oka, S., Kawamura, T., et al. (2007) Lymphatic Vessels Density at the Site of Deepest Penetration as a Predictor of Lymph Node Metastasis in Submucosal Colorectal Carcinoma. Diseases of the Colon and Rectum, 50, 13-21.

[20]   Liang, P., Hong, J.W., Ubukata, H., Liu, H.R., et al. (2006) Increased Density and Diameter of Lymphatic Vessels Correlate with Lymph Node Metastasis in Early Stage Invasive Colorectal Carcinoma. Virchows Archives, 448, 570-573.

[21]   Gao, Y., Zhang, W.X., Mu, D.B., Yuan, Y.P., et al. (2008) Distribution of Angiogenesis and Lymphangiogenesis in Gastrointestinal Intramucosal Tumors. Annuls of Surgical Oncology, 15, 1117-1123.

[22]   Longgatto-Filho, A., Pinheiro, C., Fferreira, L., Scapulatempo, C., et al. (2008) Peritumoral, But Not Intratumoral Lymphatic Vessel Density and Invasion Correlate with Colorectal Carcinoma Poor-Outcome Markers. Virchows Archives, 452, 133-138.

[23]   Minsky, B.D., Miles, C., Rich, T.A. and Ticht, A. (2008) Lymphatic Invasion Is an Independent Prognostic Factor for Survival Incolorectal Carcinoma. International Journal of Radiological Oncology and Biological Physics, 17, 311-318.

[24]   Kenny, B.C. and Jain, D. (2008) Identification of Lymphatics in within the Colonic Lamina Propria in Inflammation and Neoplasia Using the Monoclonal Antibody D2-40. Yale Journal of Biology and Medicine, 81, 103-113.

[25]   Smith, K., Jones, P., Burke, D.A. Treanor, D. and Finan, P.J. (2011) Lymphatic Vessel Distribution in the Mucosa and Submucosa and Potential Implication for T1 Colorectal Tumors. Diseases of Colon and Rectum, 54, 35-40.

[26]   Duff, S.E., Jeziorska, M., Jumar, S., Haboubi, N., et al. (2006) Lymphatic Vessel Density, Microvessel Density and Lymphagiogenic Growth Factor Expression in Colorectal Cancer. Colorectal Disease, 9, 793-8000.

[27]   Harris, E.I., Lewin, D.N., Wang, H.L., Lauwers, G.Y., Srivastava, A., Shyr, Y., et al. (2008) Lymphovascular Invasion in Colorectal Cancer: An Interobserver Variability Study. American Journal of Surgical Pathology, 32, 1816-1821.

[28]   Messenger, D.E., Driman, D.K., McLeod, R.S., Riddel, R.H. and Kirsch, R. (2011) Current Practice Patterns among Pathologists in the Assessment of Venous Invasion in Colorectal Cancer. Journal of Clinical Pathology, 64, 983-989.

[29]   Betge, J., Pollheimer, M.J., Lindtner, R.A., Kornprat, P., Schlemmer. A., et al. (2012) Intramural and Extramural Vascular Invasion in Colorectal Cancer. Cancer, 43, 628-638.

[30]   Losi, L., Ponti, G., Gregoria, C.D., Marino, M., Rossi, G., et al. (2006) Prognostic Significance of Histological Features and Biological Parameters in Stage I (pT1 and pT2) Colorectal Adenocarcinoma. Pathology Research and Practice, 202, 663-670.

[31]   Meguerditchain, A.N., Bairati, I., Lagace, R., Harel, F., Dahl, O., et al. (2005) Prognostic Significance of Lymphovascular Invasion in Surgically Cured Rectal Carcinoma. American Journal of Surgery, 189, 707-713.