title: Loss of membranous VEGFR1 expression is associated with an adverse phenotype and shortened survival in breast cancer.
abstract: Angiogenesis is a key process in tumor growth and progression, which is controlled by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). In order to better understand the prevalence and prognostic value of VEGFR1 expression in breast cancer, a tissue microarray containing >2,100 breast cancer specimens, with clinical follow‑up data, was analyzed by immunohistochemistry using an antibody directed against the membrane‑bound full‑length receptor protein. The results demonstrated that membranous VEGFR1 staining was detected in all (5 of 5) normal breast specimens. In carcinoma specimens, membranous staining was negative in 3.1%, weak in 6.3%, moderate in 10.9%, and strong in 79.7% of the 1,630 interpretable tissues. Strong staining was significantly associated with estrogen receptor and progesterone receptor expression, but was inversely associated with advanced tumor stage (P=0.0431), high Bloom-Richardson-Ellis Score for Breast Cancer grade and low Ki67 labeling index (both P<0.0001). Cancers with moderate to strong (high) VEGFR1 expression were associated with significantly improved overall survival, as compared with tumors exhibiting negative or weak (low) expression (P=0.0015). This association was also detected in the subset of nodal‑positive cancers (P=0.0018), and in the subset of 185 patients who had received tamoxifen as the sole therapy (P=0.001). In conclusion, these data indicated that membrane‑bound VEGFR1 is frequently expressed in normal and cancerous breast epithelium. In addition, reduced or lost VEGFR1 expression may serve as a marker for poor prognosis in patients with breast cancer, who might not optimally benefit from endocrine therapy.
authors.affiliation: Institute of Pathology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lebok
authors.affiliation: Institute of Pathology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Huber
authors.affiliation: Institute of Pathology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany.
authors.forename: Eike-Christian
authors.initials: EC
authors.lastname: Burandt
authors.affiliation: Institute of Pathology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Lebeau
authors.affiliation: Institute of Pathology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany.
authors.forename: Andreas Holger
authors.initials: AH
authors.lastname: Marx
authors.affiliation: Institute of Pathology, University Hospital Basel, 4056 Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.affiliation: Department of Gynaecology, Hospital Itzehoe, D-25524 Itzehoe, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Heilenkötter
authors.affiliation: Department of Gynaecology, Hospital Pinneberg, D-25421 Pinneberg, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Jänicke
authors.affiliation: Department of Gynaecology, Hospital Pinneberg, D-25421 Pinneberg, Germany.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.affiliation: Department of Gynaecology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Paluchowski
authors.affiliation: Department of Gynaecology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Geist
authors.affiliation: Department of Gynaecology, Hospital Elmshorn, D-25337 Elmshorn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wilke
authors.affiliation: Institute of Pathology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Institute of Pathology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Institute for Pathology, University of Cologne, D‑50937 Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Quaas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D002462:Cell Membrane / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D013629:Tamoxifen; D040281:Vascular Endothelial Growth Factor Receptor-1