结直肠癌淋巴管分布特点及其临床病理意义
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摘要
目的探讨结直肠癌中淋巴管的分布特点、密度与结直肠癌转移和预后的关系。方法采用免疫组织化学方法,以D2-40为淋巴管特异性标志物,对102例结直肠癌及其相应癌旁组织、正常组织进行淋巴管染色,进行微淋巴管密度分析,并检测相应组织的VEGF-D,结合结直肠癌临床病理参数和预后进行分析。结果结直肠癌中心及浅表部位淋巴管多为闭锁的条索状,边缘区淋巴管多呈管样扩张状。结直肠癌边缘区淋巴管密度(21.6±5.6)较正常结直肠组织(5.4±2.8)和癌旁组织(6.7±3.4)显著增高(P<0.01)。结直肠癌边缘区微淋巴管密度与组织学分级、淋巴管受累、淋巴结转移及远处器官转移密切相关(P<0.01或<0.05)。结论结直肠癌组织中存在新生淋巴管,且主要分布于肿瘤边缘区,癌周围淋巴管密度增加与癌细胞转移相关,结直肠癌边缘区微淋巴管密度测定可能有助于评估其淋巴结转移和判断预后,VEGF-D阳性表达在Dukes C、D期与A、B期之间存在显著性差异,表明VEGF-D在结直肠癌向浆膜层浸润或转移过程中表达升高。
Objective To investigate the relationship of the lymphatic microvessel distribution and density with lymphatic metastasis and prognosis of primary colorectal cancer. Methods 102 patients with colorectal cancer were studied. Monoclonal antibody D2-40 was used immunohistochemically to detect the lymphatic microvessel density(LMVD) of the primary colorectal cancer, peri-tumoral area of colorectal cancer and normal colorectal tissue, and analysis the relationship among the lymphatic microvessel density(LMVD), lymphatic invasion, lymph node metastasis and other clinicopathological parameters of the primary colorectal cancer. Results The shape of lymphatic microvessel in the intra-tumoral area and superfic lymphatic vessel were strip-like, while those in the peri-tumoral area were tubular distented. LMVD in the peri-tumoral area (21.6±5.6) of colorectal cancer was significantly higher than that in near tumoral area(6.7±3.4) and in nomal colorectal tissue(5.4±2.8)(P<0.01). LMVD in the peri-tumoral area of colorectal cancer was significantly associated with lymphatic invasion, lymph node metastasis and its clinical prognosis (P < 0.05). Conclusion Lymphangiogenesis occurred in human colorectal carcinomas. LMVD in the peri-tumoral area was significantly associated with lymphatic invasion and lymph node metastasis, and detection of LMVD in peri-tumoral area can be used for the prediction of lymph node metastasis and serves as a prognostic indicator for the progression of colorectal cancer.
Objective To investigate the relationship of the lymphatic microvessel distribution and density with lymphatic metastasis and prognosis of primary colorectal cancer. Methods 102 patients with colorectal cancer were studied. Monoclonal antibody D2-40 was used immunohistochemically to detect the lymphatic microvessel density(LMVD) of the primary colorectal cancer, peri-tumoral area of colorectal cancer and normal colorectal tissue, and analysis the relationship among the lymphatic microvessel density(LMVD), lymphatic invasion, lymph node metastasis and other clinicopathological parameters of the primary colorectal cancer. Results The shape of lymphatic microvessel in the intra-tumoral area and superfic lymphatic vessel were strip-like, while those in the peri-tumoral area were tubular distented. LMVD in the peri-tumoral area (21.6±5.6) of colorectal cancer was significantly higher than that in near tumoral area(6.7±3.4) and in nomal colorectal tissue(5.4±2.8)(P<0.01). LMVD in the peri-tumoral area of colorectal cancer was significantly associated with lymphatic invasion, lymph node metastasis and its clinical prognosis (P < 0.05). Conclusion Lymphangiogenesis occurred in human colorectal carcinomas. LMVD in the peri-tumoral area was significantly associated with lymphatic invasion and lymph node metastasis, and detection of LMVD in peri-tumoral area can be used for the prediction of lymph node metastasis and serves as a prognostic indicator for the progression of colorectal cancer.
引文
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4. Fidler IJ.Molecular biology of cancer:invasion and metastasis.DeVita,V.T.,Jr. Hellman,S.Rosenburg,S.A.eds.Cancer Principles and Practice of Oncology,2001,135-153 Lippincott-Raven Philadelphia.
5. van der Schaft DW , Pauwels P , Hulsmans S,et al.Absence of lymphangiogenesis in ductal breast cancer at the primary tumor site.Cancer Lett,2007;254:12836.
6. Marks A , Sutherland DR , Bailey D, et al. Characterization and distribution of an oncofetal antigen (M 2A antigen) expressed on testicular germ cell tum ours .Br J Cancer,1999,80(3-4):569-578.
7. Kahn HJ, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi's sarcoma and a subset of angiosarcomas. Mod Pathol. 2002;15:434–440.
8. Fogt F, Zimmerman RL, Ross HM, Daly T, Gausas RE. Identification of lymphatic vessels in malignant, adenomatous and normal colonic mucosa using the novel immunostain D2-40. Oncol Rep. 2004;11:47–50.
9. Stacker SA, Caesar C, Baldwin ME, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics . Nat Med, 2001;7:186-91.
10. Egashira Y, Yoshida T, Hirata I, et al. Analysis of pathological risk factors for lymph node metastasis of submucosal invasive colon cancer. Mod Pathol. 2004;17:503-511.
11. Cooper HS, Deppisch LM, Gourley WK, et al. Endoscopically removed malignant colorectal polyps: clinicopathologic correlations. Gastroenterology. 1995;108:1657-1665.
12. Hase K, Shatney CH, Mochizuki H, et al. Long-term results of curative resection of "minimally invasive" colorectal cancer. Dis Colon Rectum. 1995;38:19-26.
13. Hurlstone DP, Sanders DS, Cross SS, et al. Colonoscopic resection of lateral spreading tumours: a prospective analysis of endoscopic mucosal resection. Gut. 2004;53:1334-1339.
14. Ohno M,Nakamura T,Kunimoto Y,et al.Lymphagenesis correlates with expression of vascular endothelial growth factor-C in colorectal cancer .Oncol Rep,2003,10:939-943.
15. He Y, KarpanenT, Alitalo K. Role of lymphangiogenic factors in tumor metastasis . Biochim Biophys Acta , 2004,1654:3 - 12.
16. Schlemper RJ, Itabashi M, Kato Y, et al. Differences in the diagnostic criteria used by Japanese and Western pathologists to diagnose colorectal carcinoma. Cancer. 1998;82:60-69.
17. World Health Organization classification of tumor. Pathology and genetics of tumours of the digestive system. IARC Press 2000:105-118.
18. Dixon MF. Gastrointestinal epithelial neoplasia: Vienna revisited. Gut 2002;51:130-131.
19. Schlemper RJ, Riddell RH, Kato Y, et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 2000;47:251-255.
20. Riddell RH, Iwafuchi M. Problems arising from eastern and western classification systems for gastrointestinal dysplasia and carcinoma: are they resolvable? Histopathology 1998;33:197-202.
21. Ouchi K, Sugawara T, Ono H, et al. Histologic features and clinical significance of venous invasion in colorectal carcinoma with hepatic metastasis. Cancer. 1996;78:2313-2317.
22. Netzer P, Forster C, Biral R, et al. Risk factor assessment of endoscopically removed malignant colorectal polyps. Gut. 1998;43:669-674.
23. Sakuragi M, Togashi K, Konishi F, et al. Predictive factors for lymph node metastasis in T1 stage colorectal carcinomas. Dis Colon Rectum. 2003;46:1626-1632.
24. Ueno H, Mochizuki H, Hashiguchi Y, et al. Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology. 2004;127:385-394.
25. Tominaga K, Nakanishi Y, Nimura S, et al. Predictive histopathologic factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma. Dis Colon Rectum. 2005;48:92-100.
26. Cai J, Ikeguchi M, Maeta M, Kaibara N. Micrometastasis in lymph nodes and microinvasion of the muscularis propria in primary lesions of submucosal gastric cancer. Surgery. 2000;127:32–39.
27. Matsumoto M, Natsugoe S, Ishigami S, Nakashima S, Nakajo A, Miyazono F, Hokita S, Takao S, Eizuru Y, Aikou T. Lymph node micrometastasis and lymphatic mapping determined by reverse transcriptase–polymerase chain reaction in pN0 gastric carcinoma. Surgery. 2002;131:630–635.
28. Ishida K, Katsuyama T, Sugiyama A, Kawasaki S. Immunohistochemical evaluation of lymph node micrometastases from gastric carcinomas. Cancer. 1997;79:1069–1076.
29. Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumor lymphangiogenesis by VEGFC promotes breast cancer metastasis. Nat Med, 2001, 7(2): 192-198.
30. Yonemura Y, Endo Y, Fujita H, et al. Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer. Clin Cancer Res, 1999, 5(7): 1823-1829.
31. Parr C, Jiang WG. Quantitative analysis of lymphangiogenic markers in human colorectal cancer. Int J Oncol, 2003, 23(2): 533-539.
32. Kahn HJ, Marks A. A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors. Lab Invest. 2002;82:1255–1257.
33. Masaki T, Muto T. Predictive value of histology at the invasive margin in the prognosis of early invasive colorectal carcinoma. J Gastroenterol. 2000;35:195-200.
34. 33.J Trzewik SK,Mallipattu GM,Artmann,et al. Evidence for a second valve system in lymphatics: endothelial microvalves. FASEB J,2001,15:1711-1717.
35. Jain R K, Fenton B T. Intratumoral lymphatic vessels:a case of mistaken identity or malfunction .J Natl Cancer Inst,2002,94(6):417-421.
36. Terhi Karpanen, Kari Alitalo. Lymphatic vessels as targets of tumor therapy? .The Journal of Experimental Medicine,2001194(6):37.
37. Kitajima K, Fujimori T, Fujii S, et al. Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J Gastroenterol. 2004;39:534-543.
38. Nakamura T, Mitomi H, Kikuchi S, et al. Evaluation of the usefulness of tumor budding on the prediction of metastasis to the lung and liver after curative excision of colorectal cancer. Hepato-gastroenterology. 2005;52:1432-1435.
39. Kaneko I, Tanaka S, Oka S, et al. Lymphatic vessel density at the site of deepest penetration as a predictor of lymph node metastasis in submucosal colorectal cancer. Dis Colon Rectum. 2007;50:13
40. Okabe S, Arai T, Maruyama S, et al. A clinicopathological investigation on superficial early invasive carcinomas of the colon and rectum. Surg Today. 1998;28:687-695.
41. Padera T P,Kadambi A, di Tomaso E, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science,2002,296(5574):1883-1886
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