Clinical significance of detection on lymphatic microvessel, lymphatic microvessel density and vascular endothelial growth factor-C in patients with colorectal carcinoma

Abstract

To evaluate the clinical significance of detection on lymphatic microvessel, lymphatic microvessel density (LMVD) and vascular endothelial growth factor-C (VEGF-C) in patients with colorectal carcinoma. Eighty tissue specimens of the colorectal carcinoma and the peritumoral tissue and thirty of adjacent normal bowel tissue were collected. The lymphatic microvessel and LMVD were determined by 5'-nucleotidase histochemical staining. The expression of VEGF-C protein and VEGF-C mRNA in specimens of colorectal carcinoma and normal colorectal tissues were studied by RT-PCR and immunohistochemical methods utilizing strept-avidin-biotin complex. Clinicopathological data and survival of each patient were obtained and analyzed. (1) The brown or filemot stained lymphatic microvessels were observed in specimens from the colorectal carcinoma, the peritumoral tissue and the normal bowel. Collapsed, nonfunctional lymphatic vessels were observed in the intratumoral tissue, and plenty of lymphatic vessels with large lumen referred as functional lymphatic vessels were observed in the peritumoral tissue. (2) The mean value of LMVD in the peritumoral tissue was significantly higher than that in the normal bowel tissue (9.76+/-2.85 vs. 5.49+/-1.43, t=8.220, P<0.01) and tumor tissue (9.76+/-2.85 vs. 2.13+/-0.96, t=15.118, P<0.001). (3) The positive rate (48.8% vs. 0, P<0.01) and mean value (1.09+/-1.20 vs. 0, P<0.01) of the VEGF-C protein expression in colorectal carcinoma specimens were significantly higher than that of the normal bowel tissue. The expression of VEGF-C protein was consistent with the expression of VEGF-C mRNA. The VEGF-C expression in intratumoral tissue demonstrated significant correlation with LMVD in the peritumoral tissue of colorectal carcinoma. (4) Both LMVD in the peritumoral tissue and the expression of VEGF-C in the intratumoral tissue correlated significantly with Dukes' stage (P<0.0001 and P=0.0234), lymph node metastasis (P<0.0001 and P=0.0059), and survival (P<0.0001 and P<0.0001), but not with age, sex, location and dimension of lesion, gross and histological type. Also, there was a positive significant correlation of LMVD in the peritumoral tissue with degree of differentiation (P=0.0168) and metastasis to the liver or the lung (P=0.0088). Lymphatic microvessels in the peritumoral tissue are functional. The functional lymphatic microvessels, increased LMVD in the peritumoral tissue and the expression of VEGF-C in the intratumoral tissue may act as the morphological features and the molecular phenotype of lymphangiogenesis in colorectal carcinoma, and also as important predictive markers for evaluating lymphatic metastasis and prognosis in patients with colorectal carcinoma.