Co-determination of the angiogenic factors thymidine phosphorylase and vascular endothelial growth factor in node-negative breast cancer: Prognostic implications

被引：23

作者：

Toi M. ^{[1
]}

Gion M. ^{[2
]}

Biganzoli E. ^{[3
]}

Dittadi R. ^{[2
]}

Boracchi P. ^{[3
]}

Miceli R. ^{[3
]}

Meli S. ^{[4
]}

Mori K. ^{[5
]}

Tominaga T. ^{[1
]}

Gasparini G. ^{[6
,7
]}

机构：

[1] Department of Surgery, Tokyo Metropolitan Komagome Hospital, Tokyo

[2] Tumoral Biomarkers Laboratory, Regional Medical Centre, Venice

[3] Div. of Med. Statistics and Biometry, Ist. Naz. Stud. e la Cura del Tumori, Milan

[4] St Bortolo Regional Medical Centre, Vicenza

[5] Nippon Roche Research Centre, Kamakura, Kanagawa

[6] Azienda Ospedali Riuniti, Reggio Calabria

[7] Oncologia Medica, Azienda Ospedaliera Bianchi-M., 89100 Reggio Calabria, via Melacrino

来源：

Angiogenesis | 1997年 / 1卷 / 1期

关键词：

Angiogenesis; Breast cancer; Prognosis;

D O I：

10.1023/A:1018305132489

中图分类号：

学科分类号：

摘要：

Experimental and clinical studies have shown that human breast cancer is an angiogenesis-dependent neoplasm. In fact, several authors have demonstrated that the determination in primary tumors of the degree of vascularization (microvessel counts) as well as of some angiogenic peptides is of prognostic value. However, which are the most important mediators of angiogenesis and their relationship with other relevant biological markers needs further investigation. In the series of 260 women with node-negative breast cancer (NNBC) on which we previously assessed vascular endothelial growth factor (VEGF), we have now also determined thymidine phosphorylase (TP) protein as well as p53 protein and Cathepsin-D cytosolic levels using immunometric methods. The median concentrations of TP, p53 and Cathepsin-D were 105.4 U/mg (range 1.2-843.1), 0.22 ng/mg (range 0.0-41.65) and 33.80 nmol/mg (range 4.20-216.0), respectively. We found that TP concentrations were associated with Cathepsin-D and p53, but not with VEGF. VEGF (p < 0.0001) and p53 (p = 0.03 and p = 0.012, respectively) were found to be statistically significant prognostic variables for both relapse-free survival (RFS) and overall survival in univariate analysis. Conversely, TP and Cathepsin-D levels did not correlate with prognosis. In multivariate analysis for RFS, VEGF levels (p < 0.0001), TP levels (p = 0.050) and their first-order interaction terms (p = 0.027) were statistically significant prognostic indicators. Cathepsin-D and p53 protein levels did not retain significance in the model inclusive of all the above variables. The predictive capability of the complete model was satisfactory (Harrell c statistic = 0.72). Moreover, these results suggest a possible potentiation of the capability of predicting the likelihood of recurrence by the co-determination of TP and VEGF. The probability of recurrence was particularly high in the patients with primary tumors characterized by elevated levels of both angiogenic factors. This is the first study showing in vivo that two different angiogenic peptides concur in the progression of human breast cancer. The biology and possible therapeutic implications of this observation are discussed.

引用

页码：71 / 83

页数：12

共 43 条

[1] Gasparini G., Clinical significance of the determination of angiogenesis in human breast cancer. Update of the biological background and overview of the Vicenza studies, Eur J Cancer, 32 A, pp. 2485-2493, (1996)
[2] Ellis L.M., Fidler I.J., Angiogenesis and metastasis, Eur J Cancer, 32 A, pp. 2451-2460, (1996)
[3] Toi M., Taniguchi T., Yamamoto Y., Kurisaki T., Suzuki H., Tominaga T., Clinical significance of the determination of angiogenic factors, Eur J Cancer, 32 A, pp. 2513-2519, (1996)
[4] Page D.L., Jensen R.A., Angiogenesis in human breast carcinoma: What is the question?, Human Pathol, 26, pp. 1173-1174, (1995)
[5] Simpson J.F., Battifora H., Angiogenesis as a prognostic factor in breast cancer: Can we count on it?, Appl Immunohistochem, 3, pp. 73-74, (1995)
[6] Walker R.A., Angiogenesis and breast cancer prognosis - A continuous issue, J Pathol, 180, pp. 6-7, (1996)
[7] Vermeulen P.B., Gasparini G., Fox S.B., Et al., Quantification of angiogenesis in solid human tumours: An international consensus on the methodology and criteria of evaluation, Eur J Cancer, 32 A, pp. 2474-2484, (1996)
[8] Toi M., Kondo S., Suzuki H., Et al., Quantitative analysis on vascular endothelial growth factor in primary breast cancer, Cancer, 77, pp. 1101-1106, (1996)
[9] Gasparini G., Toi M., Gion M., Et al., Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma, J Natl Cancer Inst, 89, pp. 139-147, (1997)
[10] Nguyen M., Watanabe H., Budson A.E., Richie J.P., Hayes D.F., Folkman J., Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers, J Natl Cancer Inst, 86, pp. 356-361, (1994)

← 1 2 3 4 5 →