Angiopoietin-2 expression in breast cancer correlates with lymph node invasion and short survival.
Angiogenic factors produced by tumor cells are essential for tumor growth and metastasis. In our study, the expression of Angiopoietin-1 (ANG1) and Angiopoietin-2 (ANG2) mRNA in archival human breast cancer tumor samples and in 6 breast cancer cell lines was investigated. Total RNA from biopsies of 38 breast cancer patients was extracted and ANG1 and ANG2 mRNA expression was measured by means of quantitative real-time RT-PCR (Taqman). Matching data with available clinicopathologic and biochemical data revealed a significant association between ANG2 expression and axillary lymph node invasion. Univariate and multivariate survival analysis, by means of Kaplan-Meier method and Cox's proportional hazards model, showed significant and independent association between ANG2 mRNA level and both disease-free (p < 0.0001) and overall survival (p < 0.0003). An important fact is that, notwithstanding the small number of cases examined, this association was confirmed also in the group of lymph node-negative patients (DFS, p < 0.003; OS, p < 0.020). Immunohistochemical analysis demonstrated that Ang2 is expressed by both tumor cells and endothelial elements. Expression in tumor cells was confirmed by studying a panel of human breast carcinoma cell lines in culture by RT-PCR. In ZR75.1 and T47D cells, expression of ANG2 mRNA was increased up to 10-fold by treatment with estrogen within 24 hr. Although preliminary, these data suggest a possible role of ANG2 as a prognostic factor for primary breast cancer.
Sfiligoi
Christian
C
Institute for Cancer Research and Treatment, Laboratory of Gynecological Oncology, Str. Prov. 142, 10060 Candiolo, Turin, Italy.
de Luca
Annarita
A
Cascone
Ilaria
I
Sorbello
Valentina
V
Fuso
Luca
L
Ponzone
Riccardo
R
Biglia
Nicoletta
N
Audero
Enrica
E
Arisio
Riccardo
R
Bussolino
Federico
F
Sismondi
Piero
P
De Bortoli
Michele
M
D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis*; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality*; D018450:Disease Progression; D018572:Disease-Free Survival; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D042582:Vascular Endothelial Growth Factor C
C467630:ANGPT1 protein, human; D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D016228:Endothelial Growth Factors; D004967:Estrogens; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C