title: Hemangiomas and angiosarcomas of the breast: diagnostic utility of cell cycle markers with emphasis on Ki-67.
abstract: BACKGROUND
  Vascular tumors comprise a minor subgroup of tumors arising in the breast and represent variants of hemangiomas and angiosarcomas. Diagnostic challenges may arise when differentiating hemangiomas from types I and II angiosarcomas. Ki-67 expression has been used as an adjunct to distinguish between benign and malignant lesions exhibiting histologic overlap at various anatomic sites.
  
  
  OBJECTIVE
  To investigate the utility of Ki-67 and other cell cycle regulatory proteins (S-phase kinase-associated protein 2 [Skp2], p27, and cyclin D1) in the differential diagnosis of mammary vascular lesions.
  
  
  METHODS
  Thirty-four vascular tumors (21 hemangiomas and 13 angiosarcomas) of the breast were studied. The Ki-67 index and immunoreactivity for Skp2, p27, and cyclin D1 were determined in each case. Appropriate statistical methods were used.
  
  
  RESULTS
  The mean value of Ki-67 index was statistically different when comparing hemangiomas and angiosarcomas (P < .001). Angiosarcomas were typically positive for Skp2, whereas hemangiomas were negative (P < .001). Sensitivity and specificity cutoffs for Ki-67 index to distinguish hemangiomas from angiosarcomas showed a candidate cutoff point of 175. The mean values of Ki-67 of low-grade angiosarcomas were significantly different from all hemangiomas (P < .001) and also different from the subset of atypical hemangiomas (P = .02). Sensitivity and specificity cutoffs for Ki-67 index to distinguish all hemangiomas from low-grade angiosarcomas showed a candidate cutoff point between 150 and 175. Among angiosarcomas, positivity for Ki-67 was inversely related to that of p27 but not to Skp2 or cyclin D1. This was also true among hemangiomas.
  
  
  CONCLUSIONS
  Ki-67 index can be used as a diagnostic tool to distinguish between benign and malignant vascular lesions of the breast. This can be particularly helpful in cases of histologic overlap such as low-grade angiosarcoma and hemangioma.
authors.affiliation: Department of Pathology and Laboratory Medicine-Starr 1009, New York Presbyterian Hospital-Weill Medical College of Cornell University, 525 E 68th St, New York, NY 10021, USA. sjshin@med.cornell.edu
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Shin
authors.forename: Martin
authors.initials: M
authors.lastname: Lesser
authors.forename: Paul Peter
authors.initials: PP
authors.lastname: Rosen
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D018567:Breast Neoplasms, Male / Q000175:diagnosis* / Q000378:metabolism; D002453:Cell Cycle; D019938:Cyclin D1 / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006391:Hemangioma / Q000175:diagnosis* / Q000378:metabolism; D006394:Hemangiosarcoma / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D044786:S-Phase Kinase-Associated Proteins; C413374:p27 antigen; D019938:Cyclin D1