title: Expression and role of fibroblast activation protein-alpha in microinvasive breast carcinoma.
abstract: BACKGROUND
  Diagnosis of ductal carcinoma in situ (DCIS) in breast cancer cases is challenging for pathologist due to a variety of in situ patterns and artefacts, which could be misinterpreted as stromal invasion. Microinvasion is detected by the presence of cytologically malignant cells outside the confines of the basement membrane and myoepithelium. When malignant cells invade the stroma, there is tissue remodeling induced by perturbed stromal-epithelial interactions. Carcinoma-associated fibroblasts (CAFs) are main cells in the microenvironment of the remodeled tumor-host interface. They are characterized by the expression of the specific fibroblast activation protein-alpha (FAP-α), and differ from that of normal fibroblasts exhibiting an immunophenotype of CD34. We hypothesized that staining for FAP-α may be helpful in determining whether DCIS has microinvasion.
  
  
  METHODS
  349 excised breast specimens were immunostained for smooth muscle actin SMA, CD34, FAP-α, and Calponin. Study material was divided into 5 groups: group 1: normal mammary tissues of healthy women after plastic surgery; group 2: usual ductal hyperplasia (UDH); group 3: DCIS without microinvasion on H & E stain; group 4: DCIS with microinvasion on H & E stain (DCIS-MI), and group 5: invasive ductal carcinoma (IDC). A comparative evaluation of the four immunostains was conducted.
  
  
  RESULTS
  Our results demonstrated that using FAP-α and Calponin adjunctively improved the sensitivity of pathological diagnosis of DCIS-MI by 11.29%, whereas the adjunctive use of FAP-α and Calponin improved the sensitivity of pathological diagnosis of DCIS by 13.6%.
  
  
  CONCLUSIONS
  This study provides the first evidence that immunostaining with FAP-α and Calponin can serve as a novel marker for pathologically diagnosing whether DCIS has microinvasion.
authors: Department of Pathology, College of Basic Medicine, Southern Medical University, 510515 Guangzhou, China.
authors: Xing
authors: X
authors: Hua
authors: Lina
authors: L
authors: Yu
authors: Xiaoxiao
authors: X
authors: Huang
authors: Zexiao
authors: Z
authors: Liao
authors: Qi
authors: Q
authors: Xian
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D002278:Carcinoma in Situ / Q000175:diagnosis* / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000378:metabolism; D010450:Endopeptidases; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D018093:Gelatinases / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis*; D008840:Microfilament Proteins / Q000032:analysis / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000175:diagnosis*; D012697:Serine Endopeptidases / Q000032:analysis / Q000096:biosynthesis*; D000096985:Calponins; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D008840:Microfilament Proteins; D012697:Serine Endopeptidases; D000096985:Calponins; D000099167:Fibroblast Activation Protein Alpha