title: Damage effect of high-intensity focused ultrasound on breast cancer tissues and their vascularities.
abstract: BACKGROUND
  High-intensity focused ultrasound (HIFU) is a noninvasive therapy that makes entire coagulative necrosis of a tumor in deep tissue through the intact skin. There are many reports about the HIFU's efficacy in the treatment of patients with breast cancer, but randomized clinical trials are rare which emphasize on the systematic assessment of histological changes in the ablated tumor vascularities, while clinical trials utilizing bevacizumab and other anti-angiogenic drugs in breast cancer have not demonstrated overall survival benefit. The purpose of this study is to evaluate the damage effect of HIFU on breast cancer tissues and their vascularities.
  
  
  METHODS
  Randomized clinical trials and the modality of treat-and-resect protocols were adopted. The treated outcome of all patients was followed up in this study. The target lesions of 25 breast cancer patients treated by HIFU were observed after autopsy. One slide was used for hematoxylin-eosin (HE) staining, one slide was used for elastic fiber staining by Victoria blue and Ponceau's histochemical staining, and one slide was used for vascular endothelial cell immunohistochemical staining with biotinylated-ulex europaeus agglutinin I (UEAI); all three slides were observed under an optical microscopic. One additional slide was systematically observed by electron microscopy.
  
  
  RESULTS
  The average follow-up time was 12 months; no local recurrence or a distant metastatic lesion was detected among treated patients. Histological examination of the HE slides indicated that HIFU caused coagulative necrosis in the tumor tissues and their vascularities: all feeder vessels less than 2 mm in diameter in the insonated tumor were occluded, the vascular elasticity provided by fibrin was lost, the cells were disordered and delaminated, and UEAI staining of the target lesions was negative. Immediately after HIFU irradiation, the tumor capillary ultrastructure was destroyed, the capillary endothelium was disintegrated, the peritubular cells were cavitated, and the plasma membrane was incomplete.
  
  
  CONCLUSIONS
  HIFU ablation can destroy all proliferating tumor cells and their growing vascularities simultaneously; this may break interdependent vicious cycle of tumor angiogenesis and neoplastic cell growth that results in infinite proliferation. While it cannot cause tumor resistance to HIFU ablation, it may be a new anti-angiogenic strategy that needs further clinical observation and exploration. Furthermore, the treatment indications of HIFU ablation were reviewed and discussed in this manuscript.
authors.affiliation: Department of Obstetrics and Gynaecology, Zhabei District Central Hospital, No. 619, Zhonghuaxin Road, Zhabei District, Shanghai, 200000, China. guanliming1@126.com.
authors.forename: Liming
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Radiotherapy, Tumor Hospital, Peking University, No. 69, Wanfeng Road, Fengtai District, Beijing, 100000, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000556:secondary* / Q000628:therapy; D018275:Carcinoma, Lobular / Q000098:blood supply / Q000556:secondary* / Q000628:therapy; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D057086:High-Intensity Focused Ultrasound Ablation / Q000009:adverse effects*; D006801:Humans; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000098:blood supply / Q000473:pathology* / Q000628:therapy; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011379:Prognosis; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors
keywords: Breast cancer; High-intensity focused ultrasound; Tumor vascularities