title: Analysis of expression of membrane-bound tumor markers in ductal carcinoma in situ of the breast: paving the way for molecular imaging.
abstract: OBJECTIVE
  Achieving radicality during breast conserving surgery for pure ductal carcinoma in situ (DCIS) of the breast and invasive cancer surrounded by DCIS is challenging. Molecular imaging holds promise here, when applied as a tool for image-guided surgery of DCIS.
  
  
  METHODS
  Tissue microarrays containing 24 pure DCIS and 63 DCIS with adjacent invasive breast cancer cases were stained by immunohistochemistry for a panel of membrane-bound targets.
  
  
  RESULTS
  GLUT1 expression was present in 60.9%, IGF1-R in 55.2% HER2 in 28.7%, MET in 18.4%, EGFR in 16.1%, CD44v6 in 69%, carbonic anhydrase XII (CAXII) in 24.1% and Mammaglobin in 14.9% of DCIS cases. No expression differences between pure DCIS and DCIS with adjacent cancer were observed. Further, HER2 and EGFR expression were correlated with high grade DCIS (p=0.001) and CAXII with low grade DCIS (p=0.027). A putative panel containing HER2, EGFR, GLUT1 and IGF1-R had a detection rate of 90.2% for DCIS and 78.3% for adjacent breast cancer.
  
  
  CONCLUSIONS
  We found that membrane-bound targets are more frequently expressed in DCIS than in invasive breast cancer, but that single membrane proteins are too infrequently expressed to serve as single imaging targets for the detection of DCIS. However, a panel of markers consisting of IGF1-R, CD44v6, GLUT1, EGFR, and HER2 was found to be positive in 96.3% of DICS based on marker expression in the adjacent invasive breast cancer as described earlier. This implies that detection of DCIS based on marker expression in the adjacent invasive breast cancer during breast conserving surgery should be possible with a panel of molecular imaging tracers targeting CD44v6, GLUT1, HER2, IGF1-R, and EGFR.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
authors.forename: Jeroen F
authors.initials: JF
authors.lastname: Vermeulen
authors.forename: Elsken
authors.initials: E
authors.lastname: van der Wall
authors.forename: Arjen J
authors.initials: AJ
authors.lastname: Witkamp
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D057054:Molecular Imaging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D051272:Glucose Transporter Type 1; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; C112697:CD44v6 antigen; C495677:SLC2A1 protein, human; C512478:EGFR protein, human