Vascular endothelial growth factor (VEGF) and other common tissue prognostic indicators in breast cancer: a case-control study.
VEGF is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis in physiological and pathological conditions. Nevertheless, VEGF tissue evaluation in cancer patients as a prognostic factor compared to the conventional histological and biological parameters is still controversial. In this case-control study, tissue VEGF was retrospectively determined by immunohistochemistry and related to T, N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 in 129 breast cancer patients. Seventy-four of these patients had developed distant metastases postoperatively. The remaining 55 patients had remained disease-free >10 years after surgery. In 17 (13%) of the 129 patients (six with distant metastases and eleven disease-free) tissue and plasma VEGF were concomitantly evaluated. In univariate analysis no significant differences in VEGF and tumor size were found between metastatic and disease-free patients, whereas there were significant differences in N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 (p ranging from 0.001 to 0.0001). In multivariate analysis VEGF showed less significance than N, ER, c-erbB-2, MIB-1 and cyclin D1 (p = 0.012, p = 0.007, p = 0.005, p = 0.005, p = 0.002 and p = 0.001, respectively). VEGF was a significant unfavorable prognostic indicator only in the N+ subset (p = 0.015), while ER (p = 0.05 and p = 0.021) and MIB-1 (p = 0.031 and p = 0.022) were significant in both the N+ and N- subgroups. In multivariate analysis in the 74 metastatic cases VEGF did not show any significance in relation to disease-free interval and overall survival from the time of mastectomy and from the time of relapse, whereas N and PgR did (p ranging from 0.018 to 0.001). In conclusion, tissue VEGF does not seem a suitable candidate to replace conventional histological and other common biological prognostic factors in breast cancer.
Nicolini
A
A
Department of Internal Medicine, University of Pisa, Italy. anicolin@int.med.unipi.it
Campani
D
D
Miccoli
P
P
Spinelli
C
C
Carpi
A
A
Menicagli
M
M
Ferrari
P
P
Gadducci
G
G
Rossi
G
G
Fini
M
M
Giavaresi
G
G
Bonazzi
V
V
Giardino
R
R
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D019938:Cyclin D1 / Q000096:biosynthesis; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D012008:Recurrence; D012680:Sensitivity and Specificity; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
D014408:Biomarkers, Tumor; D019938:Cyclin D1; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A