Effects of estrogen depletion on angiogenesis in estrogen-receptor-positive breast carcinoma--an immunohistochemical study of vasohibin-1 and CD31 with correlation to pathobiological response of the patients in neoadjuvant aromatase inhibitor therapy.
OBJECTIVE
Tumor-stroma interactions, including angiogenesis, are pivotal in breast cancer. Changes of angiogenesis during endocrine therapy have not been reported in breast cancer patients. Vasohibin-1 (VASH-1) is a recently identified endothelium-derived negative feedback regulator of angiogenesis. Vasohibin-1 positive ratio (VPR) is proposed as an indicator of neovascularization of the tissues.


METHODS
The status of neovascularization, based on VPR before and after steroidal aromatase inhibitor (AI) exemestane (EXE) treatment, was evaluated in 54 post-menopausal Asian patients. VPR changes were correlated with the pathobiological response of the patients using Ki67 labeling index (LI) changes.


RESULTS
When using a decrement of more than 40% in post-treatment Ki67 LI as the definition of response, significant inverse correlation was detected between Ki67 LI and VPR changes in responders. Significant increment in neovascularization, as demonstrated by elevated VPR, was only detected in responders (p = 0.039). Increased angiogenesis detected in responders to neoadjuvant therapy may represent a stromal response to dying/dead cells, as part of tumor-stroma interaction following estrogen depletion.


CONCLUSIONS
VPR could be a potential surrogate marker for predicting neoadjuvant endocrine therapy response, incorporating features of both carcinoma and stromal cells, in the early stage of neoadjuvant endocrine therapy before any discernible clinical and/or histopathological changes became apparent.
Tohoku University School of Medicine, Department of Pathology, 2-1 Seiryou-machi, Aoba-ku, Sendai, Japan.
Monica S M
MS
Chan
Lin
L
Wang
Niramol
N
Chanplakorn
Kentaro
K
Tamaki
Takayuki
T
Ueno
Masakazu
M
Toi
Wings T Y
WT
Loo
Louis W C
LW
Chow
Takashi
T
Suzuki
Hironobu
H
Sasano
D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D020360:Neoadjuvant Therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011960:Receptors, Estrogen; C493181:VASH1 protein, human; D042461:Vascular Endothelial Growth Factor A