Study On The Relationship Between Lymphatic Vessel Density (LVD) Stained By LYVE-1 And Distal Intramural Spread(DIS) Of Rectal Cancer

Background: Lymphatic vessels play a crucial role in a variety of human cancers,since invasion of lymphatic vessels by tumor cells and subsequent development oflymph node metastases significantly influences prognosis of cancer patients. Andlymphangiogenesis is an initiating agent of the metastasis of lymphtics for themalignant cancer. In recent years, oncological research has been focused on thevascular system or angiogenesis, whereas the study of lymphangiogenesis or theformation of new lymphatic vessels has been relatively neglected, chiefly due tothe lack of means to detect or determine lymphatic vessels by specific markers.This situation has been changed rapidly recently following the discovery of somelymphangiogenic markers, such as VEGFR-3(vascular endothelial growth factorreceptor-3), Prox-1, podoplanin, LYVE-1(lymphatic vessel endothelial hyaluronanreceptor-1),D2-40 and so on. Among them, LYVE-1 maybe more effective for thespecificity to the lymphatic vessels, because its expression was not found on theblood vessels expect for the liver sinusoidat endothelia. Microlymphatic vesseldensity (LVD), a commonly applied estimate of tumor lymphangiogenesis, is anestablished prognostic factor in several malignancies, eg, breast cancer,colorectal cancer, prostate cancer, melanoma and pancreatic cancer. The smallestsafe margin of distal clearance for a lower rectal cancer is very important forradical rectectomy. In previous study, a few factors play a role in DIS, but thereare few data concerning the influence of lymphangiogenesis. We studied on therelationship between LVD and DIS of rectal cancer, analyzing the probable valueof LVD in determinating the length of distal resection of lower rectal cancer.The other clinicopathologic factors of rectal cancer were also studied.Methods: From January 2001 to August 2006, Nine-two patients who had undergone curative resection of lower rectal cancer were studied, In which 81 cases weredone with sphincter-saving operation, the rest had to be undergoneabdominoperineal resection with permanent colostomy. The length of DIS, LVD andother clinicopthological factors were evaluated. Immunohistochemical lymphaticvessel staining with LYVE-1(lymphatic vessel endothelial hyaluronan receptor-1)were performed to detecte LVD. Correlation between the LVD at peritumor and thelength of DIS of the rectal cancer was analyzed with Spearman's rank test. Therelationships between LVD and the other clinicopathological variables wereexamined with the Student's t-test or chi-square test.Results: 44 cases had DIS(range 0.1～2.44cm;mean 0.31cm), emboli of cancer inlymphatic vessels was the most common modalities of DIS. LVD of peritumoral lesionwas significantly higher than that of intratumoral lesion, LVD of DIS subgroupwas significantly higher than that of no DIS subgroup, and LVD of the two subgroupswas significantly higher than that of normal rectal tissue. A significantcorrelation was shown by a rank correlation test between the length of DIS andthe LVD at peritumor tissue of the rectal cancer (n=44, r=0. 755, p＜0.01). LVD wasalso related to the infiltration extent, lymphatic invasion and lymphatic nodemetastasis.Conclusions: Lymphangiogenesis plays an important role in rectal cancer cellmetastasis and the patients with less LVD have better prognosis. The LVD has aclose correlation with DIS. This findings may be helpful to determining the distalclearance length of rectal cancer and may have significance of clinicalapplication. LVD was related to the infiltration extent, lymphatic invasion andlymphatic node metastasis of rectal cancer, emboli of cancer was the most commonof DIS modalities. This findings suggest that rectal cancer might invade mainlythrough lymphatic vessels and lymphangiogenesis play an important role in cancercell metastasis.