title: Angiopoietin-2 expression in breast cancer correlates with lymph node invasion and short survival.
abstract: 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.
authors.affiliation: Institute for Cancer Research and Treatment, Laboratory of Gynecological Oncology, Str. Prov. 142, 10060 Candiolo, Turin, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Sfiligoi
authors.forename: Annarita
authors.initials: A
authors.lastname: de Luca
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cascone
authors.forename: Valentina
authors.initials: V
authors.lastname: Sorbello
authors.forename: Luca
authors.initials: L
authors.lastname: Fuso
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ponzone
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Biglia
authors.forename: Enrica
authors.initials: E
authors.lastname: Audero
authors.forename: Riccardo
authors.initials: R
authors.lastname: Arisio
authors.forename: Federico
authors.initials: F
authors.lastname: Bussolino
authors.forename: Piero
authors.initials: P
authors.lastname: Sismondi
authors.forename: Michele
authors.initials: M
authors.lastname: De Bortoli
mesh_terms: 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
chemical_list: 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