Prediction of metastasis risk (11 year follow-up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n=905)

Abstract

Neoangiogenesis in tumours contributes to the development of blood-borne metastases, and can be evaluated by markers of activated endothelial cells in preference to panendothelial markers. Our purpose was to document the prognostic significance of VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 immunoexpression in breast carcinoma frozen samples (n=905, follow-up=11.7 years). We observed that: (i). CD105 (P=0.001) and Tie-2/Tek (P=0.025) (but not VEGF-R1 and VEGF-R2) overexpression correlated with a shorter survival, and were (Cox's model) independent histoprognostic indicators; (ii). only CD105 marked expression correlated (P=0.035) with a shorter survival of node-negative patients; (iii). three markers - CD105 (P=0.001), Tie-2/Tek (P=0.01), VEGF-R1 (P=0.001), but not VEGF-R2 - correlated with metastatic risk in node-negative patients in univariate analysis; and (iv). VEGF-R1 (P=0.01) expression correlated with high local recurrence risk. It is concluded that CD105 and to a lesser extent Tie-2/Tek and VEGF-R1, but not VEGF-R2 are endowed with prognostic significance that may be useful for patient monitoring, particularly CD105 expression for selecting node-negative patients for more aggressive postsurgery therapy.

Figure 1

Kaplan–Meier survivorship plot of metastasis-free survival: a greater risk of metastasis was found (P=0.03, not shown) for patients with tumours in which VEGF-R1-stained surface was greater (cutoff 5%), and more specifically in node-negative patients (p=0.001).

Figure 2

Kaplan–Meier survivorship plot of recurrence-free survival: a greater risk of recurrence was found in which VEGF-R1-stained surface within tumours was greater in node-negative patients (P=0.01).

Figure 3

Kaplan–Meier survivorship plot of overall patients (but not for node-negative patients) with breast carcinomas: a greater risk of death was found for patients with tumours in which 7% or more of the tumour stained surface was Tie-2/Tek positive (P=0.025).

Figure 4

Kaplan–Meier univariate analysis showing a higher risk of metastasis in node-negative patient with tumours in which Tie-2/Tek stained surface was larger than 7% (P=0.01).

Figure 5

Kaplan–Meier univariate analysis showing a higher risk of death in node-negative patients (P=0.035) with a number of CD105 positive ⩾15 within tumours.

Figure 6

Kaplan–Meier univariate analysis showing a higher risk of metastasis in node-negative patients (P=0.001) with a number of CD105 positive ⩾15 within tumours.