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Diseases of the Colon & Rectum
Published in: Diseases of the Colon & Rectum 1/2007

01-01-2007

Lymphatic Vessel Density at the Site of Deepest Penetration as a Predictor of Lymph Node Metastasis in Submucosal Colorectal Cancer

Authors: Iwao Kaneko, M.D., Shinji Tanaka, M.D., Ph.D., Shiro Oka, M.D., Toru Kawamura, M.D., Toru Hiyama, M.D., Masanori Ito, M.D., Masaharu Yoshihara, M.D., Fumio Shimamoto, M.D., Kazuaki Chayama, M.D.

Published in: Diseases of the Colon & Rectum | Issue 1/2007

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Purpose

Lymph node metastasis is an important factor that influences curability after endoscopic treatment of submucosal colorectal cancer. This study was designed to determine the usefulness of identification of lymphatic vessels by immunohistochemistry in predicting lymph node metastasis of submucosal colorectal cancer.

Methods

Lymphatic involvement was assessed by hematoxylin and eosin staining and podoplanin immunostaining on samples resected from 268 patients with submucosal colorectal cancer. Lymphatic vessel density was estimated by two investigators by average count of three fields (×200) in the area of greatest number of podoplanin-positive capillaries at the site of deepest submucosal penetration. Relations with other clinicopathologic parameters also were investigated.

Results

Lesions with high lymphatic vessel density (≥9 vessels per field) showed a significantly greater incidence of lymph node metastasis than did those with low lymphatic vessel density (<9 vessels per field; 23.3 vs. 8.4 percent). By multivariate analysis, lymphatic vessel density was determined to be an independent risk factor for lymph node metastasis of submucosal colorectal cancer (P = 0.0044). Lymphatic vessel density also correlated with tumor budding and the degree of inflammation at the invasive front.

Conclusions

Identification of lymphatic vessels by podoplanin immunostaining provides objective and accurate evaluation of lymphatic involvement. Lymphatic vessel density at the site of deepest penetration is a useful predictor of lymph node metastasis of submucosal colorectal cancer.
Literature
1.
Karita, M, Tada, M, Okita, K, Kodama, T 1991Endoscopic therapy for early colon cancer: the strip biopsy resection techniqueGastrointest Endosc37128132PubMed
2.
Kudo, S 1993Endoscopic mucosal resection of flat and depressed types of early colorectal cancerEndoscopy25455461PubMedCrossRef
3.
Tanaka, S, Haruma, K, Oh-e, H,  et al. 2000Conditions of curability after endoscopic resection for colorectal carcinoma with submucosally massive invasionOncol Rep7783788PubMed
4.
Ueno, H, Mochizuki, H, Hashiguchi, Y,  et al. 2004Risk factors for an adverse outcome in early invasive colorectal carcinomaGastroenterology127385394PubMedCrossRef
5.
Egashira, Y, Yoshida, T, Hirata, I,  et al. 2004Analysis of pathological risk factors for lymph node metastasis of submucosal invasive colon cancerMod Pathol17503511PubMedCrossRef
6.
Kitajima, K, Fujimori, T, Fujii, S,  et al. 2004Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative studyJ Gastroenterol39534543PubMedCrossRef
7.
Kyzer, S, Begin, LR, Gordon, PH, Mitmaker, B 1992The care of patients with colorectal polyps that contain invasive adenocarcinoma. Endoscopic polypectomy or colectomy?Cancer7020442050PubMedCrossRef
8.
Minamoto, T, Mai, M, Ogino, T,  et al. 1993Early invasive colorectal carcinomas metastatic to the lymph node with attention to their nonpolypoid developmentAm J Gastroenterol8810351039PubMed
9.
Tanaka, S, Yokota, T, Saito, D, Okamoto, S, Oguro, Y, Yoshida, S 1995Clinicopathologic features of early rectal carcinoma and indications for endoscopic treatmentDis Colon Rectum38959963PubMedCrossRef
10.
Tanaka, S, Haruma, K, Teixeira, CR,  et al. 1995Endoscopic treatment of submucosal invasive colorectal carcinoma with special reference to risk factors for lymph node metastasisJ Gastroenterol30710717PubMedCrossRef
11.
Tanaka, S, Haruma, K, Tatsuta, S,  et al. 1995Proliferating cell nuclear antigen expression correlates with the metastatic potential of submucosal invasive colorectal carcinomaOncology52134139PubMedCrossRef
12.
Birner, P, Obermair, A, Schindl, M, Kowalski, H, Breitenecker, G, Oberhuber, G 2001Selective immunohistochemical staining of blood and lymphatic vessels reveals independent prognostic influence of blood and lymphatic vessel invasion in early-stage cervical cancerClin Cancer Res79397PubMed
13.
Breiteneder-Geleff, S, Soleiman, A, Kowalski, H,  et al. 1999Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endotheliumAm J Pathol154385394PubMed
14.
Furudoi, A, Tanaka, S, Haruma, K,  et al. 2002Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinomaOncology62157166PubMedCrossRef
15.
Oh-e, H, Tanaka, S, Kitadai, Y, Shimamoto, F, Yoshihara, M, Haruma, K 2001Angiogenesis at the site of deepest penetration predicts lymph node metastasis of submucosal colorectal cancerDis Colon Rectum4411291136PubMedCrossRef
16.
Teixeira, CR, Tanaka, S, Haruma, K, Yoshihara, M, Sumii, K, Kajiyama, G 1994Proliferating cell nuclear antigen expression at the invasive tumor margin predicts malignant potential of colorectal carcinomasCancer73575579PubMedCrossRef
17.
Furudoi, A, Tanaka, S, Haruma, K,  et al. 2001Clinical significance of human erythrocyte glucose transporter 1 expression at the deepest invasive site of advanced colorectal carcinomaOncology60162169PubMedCrossRef
18.
Hiraga, Y, Tanaka, S, Haruma, K,  et al. 1998Immunoreactive MUC1 expression at the deepest invasive portion correlates with prognosis of colorectal cancerOncology55307319PubMedCrossRef
19.
Aoki, R, Tanaka, S, Haruma, K,  et al. 1998MUC-1 expression as a predictor of the curative endoscopic treatment of submucosally invasive colorectal carcinomaDis Colon Rectum4112621272PubMedCrossRef
20.
Teixeira, CR, Tanaka, S, Haruma, K,  et al. 1993The clinical significance of the histologic subclassification of colorectal carcinomaOncology50495499PubMedCrossRef
21.
Oh-e, H, Tanaka, S, Kitadai, Y, Shimamoto, F, Yoshihara, M, Haruma, K 2001Cathepsin D expression as a possible predictor of lymph node metastasis in submucosal colorectal cancerEur J Cancer37180188PubMedCrossRef
22.
Kaio, E, Tanaka, S, Kitadai, Y,  et al. 2003Clinical significance of angiogenic factor expression at the deepest invasive site of advanced colorectal carcinomaOncology646173PubMedCrossRef
23.
Galindo-Gallego, M, Fernandez-Acenero, MJ, Sanz-Ortega, J, Aljama, A, Lopez-Elzaurdia, C 2000Prognostic significance of microvascular counts in rectal carcinomaPathol Res Pract196607612PubMed
24.
Galindo Gallego, M, Fernandez Acenero, MJ, Sanz Ortega, J, Aljama, A 2000Vascular enumeration as a prognosticator for colorectal carcinomaEur J Cancer365560PubMedCrossRef
25.
Matsuura, T, Fukuda, Y, Fujitaka, T, Nishisaka, T, Sakatani, T, Ito, H 2000Preoperative treatment with tegafur suppositories enhances apoptosis and reduces the intratumoral microvessel density of human colorectal carcinomaCancer8810071015PubMedCrossRef
26.
Shields, JD, Borsetti, M, Rigby, H,  et al. 2004Lymphatic density and metastatic spread in human malignant melanomaBr J Cancer90693700PubMedCrossRef
27.
Kitadai, Y, Kodama, M, Cho, S,  et al. 2005Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodesInt J Cancer115388392PubMedCrossRef
28.
Sedivy, R, Beck-Mannagetta, J, Haverkampf, C, Battistutti, W, Honigschnabl, S 2003Expression of vascular endothelial growth factor-C correlates with the lymphatic microvessel density and the nodal status in oral squamous cell cancerJ Oral Pathol Med32455460PubMedCrossRef
29.
Nakamura, Y, Yasuoka, H, Tsujimoto, M,  et al. 2005Lymph vessel density correlates with nodal status, VEGF-C expression, and prognosis in breast cancerBreast Cancer Res Treat91125132PubMedCrossRef
30.
Renyi-Vamos, F, Tovari, J, Fillinger, J,  et al. 2005Lymphangiogenesis correlates with lymph node metastasis, prognosis, and angiogenic phenotype in human non-small cell lung cancerClin Cancer Res1173447353PubMedCrossRef
31.
Zeng, Y, Opeskin, K, Horvath, LG, Sutherland, RL, Williams, ED 2005Lymphatic vessel density and lymph node metastasis in prostate cancerProstate65222230PubMedCrossRef
32.
Hamilton SR, Aaltonen LA, eds. World Health Organization classification of tumours: pathology and genetics of tumours of the digestive system. Lyon, France: IARC Press, 2000:104–19
33.
Weidner, N, Semple, JP, Welch, WR, Folkman, J 1991Tumor angiogenesis and metastasis–correlation in invasive breast carcinomaN Engl J Med32418PubMedCrossRef
34.
Valencak, J, Heere-Ress, E, Kopp, T, Schoppmann, SF, Kittler, H, Pehamberger, H 2004Selective immunohistochemical staining shows significant prognostic influence of lymphatic and blood vessels in patients with malignant melanomaEur J Cancer40358364PubMedCrossRef
35.
Liang, P, Hong, JW, Ubukata, H,  et al. 2005Myofibroblasts correlate with lymphatic microvessel density and lymph node metastasis in early-stage invasive colorectal carcinomaAnticancer Res2527052712PubMed
36.
Geleff, S, Schoppmann, SF, Oberhuber, G 2003Increase in podoplanin-expressing intestinal lymphatic vessels in inflammatory bowel diseaseVirchows Arch442231237PubMed
37.
Fogt, F, Pascha, TL, Zhang, PJ, Gausas, RE, Rahemtulla, A, Zimmerman, RL 2004Proliferation of D2-40-expressing intestinal lymphatic vessels in the lamina propria in inflammatory bowel diseaseInt J Mol Med13211214PubMed
38.
Klintrup, K, Makinen, JM, Kauppila, S,  et al. 2005Inflammation and prognosis in colorectal cancerEur J Cancer4126452654PubMedCrossRef
39.
Sacchi, G, Weber, E, Agliano, M,  et al. 2003Lymphatic vessels in colorectal cancer and their relation with inflammatory infiltrateDis Colon Rectum464047PubMedCrossRef
40.
Powell, DW, Adegboyega, PA, Mari, JF, Mifflin, RC 2005Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in development, repair, and cancerAm J Physiol Gastrointest Liver Physiol289G2G7PubMedCrossRef
41.
Shao, J, Sheng, GG, Mifflin, RC, Powell, DW, Sheng, H 2006Roles of myofibroblasts in prostaglandin E2-stimulated intestinal epithelial proliferation and angiogenesisCancer Res15846855CrossRef
42.
Grutzkau, A, Kruger-Krasagakes, S, Baumeister, H,  et al. 1998Synthesis, storage, and release of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) by human mast cells: implications for the biological significance of VEGF206Mol Biol Cell9875884PubMed
43.
Fan, L, Iseki, S 1999Immunohistochemical localization of vascular endothelial growth factor in the globule leukocyte/mucosal mast cell of the rat respiratory and digestive tractsHistochem Cell Biol1111321PubMedCrossRef
44.
Hase, K, Shatney, C, Johnson, D, Trollope, M, Vierra, M 1993Prognostic value of tumor “budding” in patients with colorectal cancerDis Colon Rectum36627635PubMedCrossRef
45.
Hase, K, Shatney, CH, Mochizuki, H,  et al. 1995Long-term results of curative resection of “minimally invasive” colorectal cancerDis Colon Rectum381926PubMedCrossRef
46.
Park, KJ, Choi, HJ, Roh, MS, Kwon, HC, Kim, C 2005Intensity of tumor budding and its prognostic implications in invasive colon carcinomaDis Colon Rectum4815971602PubMedCrossRef
47.
Masaki, T, Matsuoka, H, Sugiyama, M,  et al. 2001Matrilysin (MMP-7) as a significant determinant of malignant potential of early invasive colorectal carcinomasBr J Cancer8413171321PubMedCrossRef
48.
Sordat, I, Rousselle, P, Chaubert, P,  et al. 2000Tumor cell budding and laminin-5 expression in colorectal carcinoma can be modulated by the tissue micro-environmentInt J Cancer88708717708–17 [erratum in Int J Cancer 2001; 91:900–1]PubMedCrossRef
49.
Masaki, T, Goto, A, Sugiyama, M,  et al. 2001Possible contribution of CD44 variant 6 and nuclear beta-catenin expression to the formation of budding tumor cells in patients with T1 colorectal carcinomaCancer9225392546PubMedCrossRef
50.
Masaki, T, Sugiyama, M, Matsuoka, H,  et al. 2003Coexpression of matrilysin and laminin-5 gamma2 chain may contribute to tumor cell migration in colorectal carcinomasDig Dis Sci4812621267PubMedCrossRef
51.
Jung, A, Schrauder, M, Oswald, U,  et al. 2001The invasion front of human colorectal adenocarcinomas shows co-localization of nuclear beta-catenin, cyclin D1, and p16INK4A and is a region of low proliferationAm J Pathol15916131617PubMed
52.
Makino, M, Yamane, N, Taniguchi, T, Honboh, T, Kurayoshi, K, Kaibara, N 2000p53 as an indicator of lymph node metastases in invasive early colorectal cancerAnticancer Res2020552059PubMed
53.
Jass, JR, Barker, M, Fraser, L,  et al. 2003APC mutation and tumour budding in colorectal cancerJ Clin Pathol566973PubMedCrossRef
Metadata
Title
Lymphatic Vessel Density at the Site of Deepest Penetration as a Predictor of Lymph Node Metastasis in Submucosal Colorectal Cancer
Authors
Iwao Kaneko, M.D.
Shinji Tanaka, M.D., Ph.D.
Shiro Oka, M.D.
Toru Kawamura, M.D.
Toru Hiyama, M.D.
Masanori Ito, M.D.
Masaharu Yoshihara, M.D.
Fumio Shimamoto, M.D.
Kazuaki Chayama, M.D.
Publication date
01-01-2007
Publisher
Springer-Verlag
Published in
Diseases of the Colon & Rectum / Issue 1/2007
Print ISSN: 0012-3706
Electronic ISSN: 1530-0358
DOI
https://doi.org/10.1007/s10350-006-0745-5

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