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Loss of membranous VEGFR1 expression is associated with an adverse phenotype and shortened survival in breast cancer.

Lebok P, Huber J, Burandt EC, Lebeau A, Marx AH, Terracciano L, Heilenkötter U, Jänicke F, Müller V, Paluchowski P, Geist S, Wilke C, Simon R, Sauter G, Quaas A - Mol Med Rep (2016)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Prognostic significance of vascular endothelial growth factor receptor 1 staining in (A) all cancers of no special type (NST), (B) in all NST cancers grouped according to low (negative and weak) and high (moderate and strong) staining, (C) in the subset of nodal-negative NST cancers, (D) in the subset of nodal-positive NST cancers, and (E) in the subset of 185 patients with breast cancer that received tamoxifen monotherapy.
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f3-mmr-14-02-1443: Prognostic significance of vascular endothelial growth factor receptor 1 staining in (A) all cancers of no special type (NST), (B) in all NST cancers grouped according to low (negative and weak) and high (moderate and strong) staining, (C) in the subset of nodal-negative NST cancers, (D) in the subset of nodal-positive NST cancers, and (E) in the subset of 185 patients with breast cancer that received tamoxifen monotherapy.

Mentions: To exclude a potential influence of the histological subtype on patient prognosis, survival analysis was limited to the largest subset of 1,144 carcinomas of NST with interpretable VEGFR1 IHC data. Since tumors with moderate or strong staining exhibited improved overall survival compared with tumors with negative or weak staining (P=0.0054; Fig. 3A), all NST specimens were grouped into subsets with low (i.e. negative or weak) or high (i.e. moderate or strong) staining for further survival analyses. According to these groups, tumors with high VEGFR1 staining exhibited superior overall survival in all subsets of NST (P=0.0015; Fig. 3B). This association was also true for subsets of nodal-negative NST (pN0, P=0.0256; Fig. 3C) and nodal-positive NST (pN1-2, P=0.0018; Fig. 3D). Additional analysis in a subset of 185 patients with breast cancer who had received tamoxifen monotherapy revealed a significant association between high levels of VEGFR1 and prolonged survival after treatment (P=0.0010; Fig. 3E).


Loss of membranous VEGFR1 expression is associated with an adverse phenotype and shortened survival in breast cancer.

Lebok P, Huber J, Burandt EC, Lebeau A, Marx AH, Terracciano L, Heilenkötter U, Jänicke F, Müller V, Paluchowski P, Geist S, Wilke C, Simon R, Sauter G, Quaas A - Mol Med Rep (2016)

Prognostic significance of vascular endothelial growth factor receptor 1 staining in (A) all cancers of no special type (NST), (B) in all NST cancers grouped according to low (negative and weak) and high (moderate and strong) staining, (C) in the subset of nodal-negative NST cancers, (D) in the subset of nodal-positive NST cancers, and (E) in the subset of 185 patients with breast cancer that received tamoxifen monotherapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940099&req=5

f3-mmr-14-02-1443: Prognostic significance of vascular endothelial growth factor receptor 1 staining in (A) all cancers of no special type (NST), (B) in all NST cancers grouped according to low (negative and weak) and high (moderate and strong) staining, (C) in the subset of nodal-negative NST cancers, (D) in the subset of nodal-positive NST cancers, and (E) in the subset of 185 patients with breast cancer that received tamoxifen monotherapy.
Mentions: To exclude a potential influence of the histological subtype on patient prognosis, survival analysis was limited to the largest subset of 1,144 carcinomas of NST with interpretable VEGFR1 IHC data. Since tumors with moderate or strong staining exhibited improved overall survival compared with tumors with negative or weak staining (P=0.0054; Fig. 3A), all NST specimens were grouped into subsets with low (i.e. negative or weak) or high (i.e. moderate or strong) staining for further survival analyses. According to these groups, tumors with high VEGFR1 staining exhibited superior overall survival in all subsets of NST (P=0.0015; Fig. 3B). This association was also true for subsets of nodal-negative NST (pN0, P=0.0256; Fig. 3C) and nodal-positive NST (pN1-2, P=0.0018; Fig. 3D). Additional analysis in a subset of 185 patients with breast cancer who had received tamoxifen monotherapy revealed a significant association between high levels of VEGFR1 and prolonged survival after treatment (P=0.0010; Fig. 3E).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany.

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.

No MeSH data available.


Related in: MedlinePlus