Clinical implication of expression of vascular endothelial growth factor-C in metastatic lymph nodes of uterine cervical cancers

Abstract

Vascular endothelial cell growth factor (VEGF)-C levels were significantly (P<0.05) increased in 24 out of 40 metastatic lymph node lesions of uterine cervical cancers. The prognosis of the 24 patients with increased VEGF-C level in metastatic lymph node lesions was poor and the 24-month survival rate was 38%, while the rate of the 16 patients with no change in VEGF-C level in metastatic lymph node lesions was 81%. There was a significant (P<0.01) difference in the 24-month survival rates between the two groups. This is novel, direct evidence that VEGF-C might contribute to the aggressive lymphangitic metastasis in uterine cervical cancers, and that the increase in VEGF-C level from primary tumour to metastatic lymph node might be a prognostic indicator.

Figure 1

Tumour diameter of all cases. Alive and deceased cases are numbered in ○ and •, respectively.

Figure 2

Immunohistochemical staining for VEGF-C in primary tumour and metastatic lymph node lesion in a representative case of uterine cervical cancer (original magnification × 200). A case of large cell nonkeratinising squamous cell carcinoma of the uterine cervix, metastatic lesion in cardinal lymph nodes. The addition of the first antibody, goat anti-human VEGF-C antibody, was omitted in the protocols for negative controls of VEGF-C.

Figure 3

VEGF-C histoscores in primary tumour and in metastatic lymph node lesion of uterine cervical cancers. VEGF-C histoscores were determined as described in Materials and methods. In the primary tumours and corresponding metastatic lymph node lesions, alive and deceased cases are numbered in ○ and •, respectively. Bold lines, increased significantly (P< 0.05 vs each primary tumour) from the primary tumour to the corresponding metastatic lymph node lesion. Broken lines, no significant change between the primary tumour and the corresponding metastatic lymph node lesion.

Figure 4

VEGF-C levels in primary tumour and metastatic lymph node lesions of uterine cervical cancers. VEGF-C levels were determined using a VEGF-C ELISA kit (MBL, Nagoya, Japan). Each level is the mean±s.d. of nine determinations from three parts of the same tissue in triplicate. In the primary tumours and the corresponding metastatic lymph node lesions, alive and deceased cases are numbered in ○ and •, respectively. Bold lines, increased significantly (P<0.05 vs each primary tumour) from the primary tumour to the corresponding metastatic lymph node lesion. Broken lines, no change between the primary tumour and the corresponding metastatic lymph node lesion.

Figure 5

Correlation between VEGF-C levels and VEGF-C histoscores in primary tumour and metastatic lymph node lesions of uterine cervical cancers. Alive and deceased cases in the primary tumours are numbered in ○ and •, respectively. Alive and deceased cases in the metastatic lymph nodes are numbered in □ and ▪, respectively.

Figure 6

Survival rate after curative resection for uterine cervical cancers. Patient prognosis was analysed with a 24-month survival rate. Increased, the cases with significantly increased VEGF-C level from the primary tumour to the metastatic lymph node lesion; not increased, the cases with no change in VEGF-C level from the primary tumour to the metastatic lymph node lesion.