title: Loss of annexin A1 expression in breast cancer progression.
abstract: BACKGROUND
  Annexin A1 (ANXA1) is a potential marker of development of breast cancer. However, previous studies of ANXA1 expression in primary breast carcinoma and lymph node metastasis have yielded conflicting results. Therefore, to accurately characterize the ANXA1 expression pattern, we used microarray analysis and matched patient samples to evaluate progressive alterations in ANXA1 protein expression during malignant transformation and metastasis.
  
  
  METHODS
  We constructed a tissue microarray using 82 pairs of primary breast cancers and lymph node metastases from archival materials. We also identified 21 cases of breast carcinoma for which a single slide contained the entire progression from benign breast tissue, carcinoma in situ, to invasive carcinoma. Immunohistochemical staining for ANXA1 and various prognostic markers was performed.
  
  
  RESULTS
  Microarray analysis revealed that ANXA1 expression was lost in 79% of breast carcinomas, and there was no difference in ANXA1 expression between primary breast carcinoma and lymph node metastasis. Most ANXA1-negative tumors were positive for estrogen and progesterone receptors but negative for HER2/neu and epidermal growth factor receptor. In contrast, most ANXA1-positive tumors were negative for estrogen, progesterone, and HER2/neu. In the whole tissue sections, ANXA1 is heterogeneously expressed in benign epithelium and is lost in both in situ carcinoma and invasive carcinoma.
  
  
  CONCLUSIONS
  The lack of ANXA1 expression in the majority of breast carcinomas and the early loss of ANXA1 expression in in situ carcinoma, which is maintained in both invasive and metastatic tumors, suggests a possible role for ANXA1 in the early events of malignant transformation.
authors.affiliation: Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Marcia
authors.initials: M
authors.lastname: Edelweiss
authors.forename: Banu
authors.initials: B
authors.lastname: Arun
authors.forename: Daniel
authors.initials: D
authors.lastname: Rosen
authors.forename: Erika
authors.initials: E
authors.lastname: Resetkova
authors.forename: Yun
authors.initials: Y
authors.lastname: Wu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.forename: Aysegul
authors.initials: A
authors.lastname: Sahin
authors.forename: Constance T
authors.initials: CT
authors.lastname: Albarracin
mesh_terms: D017305:Annexin A1 / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism
chemical_list: D017305:Annexin A1; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human