title: Expression and diagnostic values of calretinin and CK5/6 in cholangiocarcinoma.
abstract: BACKGROUND
  Mesothelin, a mesothelial marker, has been found expressed in and as a potential treatment target of cholangioacarcinoma (CC). It is possible that CC may be derived from the cells sharing mesothelial markers. However, the expression of other mesothelial markers in CC is largely unknown.
  
  
  METHODS
  Thirty CC cases (10 extrahepatic and 20 intrahepatic) were retrieved from our institutional archive. The immunohistochemical study of Calretinin (DC8), WT1 (6F-H2), Lymphatic Endothelial Marker (D2-40), CK5/6 (D5/16 B4) and CK19 (b170) was done on formalin fixed paraffin embedded sections for 2-3 blocks of each case. We compared the expression levels between CC and normal bile duct (NBD) on the same block.
  
  
  RESULTS
  All of the CC and NBD are positive for CK19 (23/23) and negative for WT1 (0/23) and D2-40 (0/23), except one CC positive for D2-40(1/30, 3.3%) and one NBD positive for WT1 (1/23, 4.3%). Calretinin immunoreactivity was detected in 52.2% (12/23) of CC, but none in NBD (0/23). CK5/6 was also detectable in 73.3% (22/30) of CC and all NBD (30/30). Increased expression of calretinin and reduced expression of CK5/6 were more likely associated with CC than NBD (P < 0.001 and P = 0.002, respectively). The sequential staining pattern of positive calretinin and negative CK5/6 in calretinin negative cases has a sensitivity of 69.57% and a specificity of 100% for differentiating CC from NBD. CK5/6 expression was also more likely associated with well-differentiated CC (7/7 versus 12/20 in moderately differentiated, and 9/10 in poorly differentiated, P = 0.019) and extrahepatic CC (10/10 versus 12/20 in intrahepatic, P = 0.029), but there was no association between the calretinin expression and the CC grade or location.
  
  
  CONCLUSIONS
  Calretinin and CK5/6 immunohistochemical stains may be useful for diagnosing a CC. Their immunohistochemical results should be interpreted with caution in the cases with differential diagnoses of mesothelioma and CC. A full mesothelioma panel, including WT1 and/or D2-40, is recommended to better define a mesothelial lineage. The biology of calretinin and CK5/6 expression in CC is unclear, but might shed light on identifying therapeutic targets for CC.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Pearlman School of Medicine, Philadelphia, PA, USA ; Departments of Pathology, University Medical Center of Princeton at Plainsboro/Rutgers Robert Wood Johnson Medical School, Plainsboro, NJ, USA ; Department of Chemical Biology, Ernest Mario School of Pharmacy, Department of Pathology and Lab Medicine, Robert Wood Johnson Medical School, and Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ, USA.
authors.forename: Lanjing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Pearlman School of Medicine, Philadelphia, PA, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Frank
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Pearlman School of Medicine, Philadelphia, PA, USA.
authors.forename: Emma E
authors.initials: EE
authors.lastname: Furth
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Pearlman School of Medicine, Philadelphia, PA, USA.
authors.forename: Amy F
authors.initials: AF
authors.lastname: Ziober
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Pearlman School of Medicine, Philadelphia, PA, USA.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: LiVolsi
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Pearlman School of Medicine, Philadelphia, PA, USA ; Department of Pathology, 6 Founders, 3400 Spruce St, Philadelphia, PA 19104, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Zhang
keywords: CK5/6 and immunohistochemistry; Calretinin; Cholangiocarcinoma; Differentiation