Lymphangiogenic and angiogenic microvessel density in human primary sporadic colorectal carcinoma

Abstract

Aim: To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma (SCRC) and their relationship to metastasis and prognosis.

Methods: The lymphatic vessel density (LVD) and microvessel density (MVD) in tumor tissue obtained from 132 patients with primary SCRC, including 74 with metastases and 58 without metastases, were evaluated by immunohistochemistry using antibodies directed against D2-40 and von Willebrand factor (vWF).

Results: (1) The lymphatic vessels and microvessels at central portions of SCRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at tumor borders had large and open lumina. The LVD and MVD were both obviously higher in colorectal cancer patients with metastases than in those without (P < 0.001). (2) For each one lymphatic vessel increased, there was a 1.45-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of LVD in predicting metastasis or non-metastasis in SCRC were 71.62% and 56.90%, respectively, and the corresponding LVD was 5. For each one microvessel increased, there was a 1.11-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of MVD were 66.22% and 51.72%, respectively. (3) Double labeling immunohistochemistry showed D2-40 immunoreactivity to be specific for lymphatic vessels. (4) Univariate analysis indicated that high LVD, high MVD, as well as co-accounting of high LVD and high MVD were associated with patient's poor disease-free survival (Puni < 0.05); multivariate analysis indicated that co-accounting of LVD and MVD was an independent prognostic factor of colorectal cancer.

Conclusion: D2-40 is a new specific antibody for lymphatic endothelial cells. Lymphogenesis and angiogenesis are commonly seen in SCRC, especially at tumor borders. The detection of LVD and MVD at tumor borders may be useful in predicting metastasis and prognosis in patients with SCRC, and, in particular, co-accounting of LVD and MVD might be a useful prognostic factor in SCRC.

Figure 1

Immunohistochemical stainings of D2-40 (A, B, C × 100), vWF (D, E × 100) and double labeling immunohistochemistry (F × 200, red: Blood vessels labled by vWF; amethyst: Lymphatic vessels by D2-40). A: Lymphangioma (positive control); B-F: Colorectal carcinoma.

Figure 2

ROC curve of LVD (A) and MVD (B).

Figure 3

Survival curve of LVD (A), MVD (B) and co-accounting of LVD and MVD (C).