title: Cholangiocarcinoma: Correlation between Molecular Profiling and Imaging Phenotypes.
abstract: OBJECTIVE
  To investigate associations between imaging features of cholangiocarcinoma by visual assessment and texture analysis, which quantifies heterogeneity in tumor enhancement patterns, with molecular profiles based on hypoxia markers.
  
  
  METHODS
  The institutional review board approved this HIPAA-compliant retrospective study of CT images of intrahepatic cholangiocarcinoma, obtained before surgery. Immunostaining for hypoxia markers (EGFR, VEGF, CD24, P53, MDM2, MRP-1, HIF-1α, CA-IX, and GLUT1) was performed on pre-treatment liver biopsies. Quantitative imaging phenotypes were determined by texture analysis with gray level co-occurrence matrixes. The correlations between quantitative imaging phenotypes, qualitative imaging features (measured by radiographic inspection alone), and expression levels of the hypoxia markers from the 25 tumors were assessed.
  
  
  RESULTS
  Twenty-five patients were included with a median age of 62 years (range: 54-84). The median tumor size was 10.2 cm (range: 4-14), 10 (40%) were single tumors, and 90% were moderately differentiated. Positive immunostaining was recorded for VEGF in 67% of the cases, EGFR in 75%, and CD24 in 55%. On multiple linear regression analysis, quantitative imaging phenotypes correlated significantly with EGFR and VEGF expression levels (R2 = 0.4, p<0.05 and R2 = 0.2, p<0.05, respectively), while a trend was demonstrated with CD24 expression (R2 = 0.33, p = 0.1). Three qualitative imaging features correlated with VEGF and CD24 expression (P<0.05), however, none of the qualitative features correlated with the quantitative imaging phenotypes.
  
  
  CONCLUSIONS
  Quantitative imaging phenotypes, as defined by texture analysis, correlated with expression of specific markers of hypoxia, regardless of conventional imaging features.
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Eran
authors.initials: E
authors.lastname: Sadot
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Simpson
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Richard K G
authors.initials: RK
authors.lastname: Do
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gonen
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: T Peter
authors.initials: TP
authors.lastname: Kingham
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000235:genetics*; D001653:Bile Ducts, Intrahepatic / Q000000981:diagnostic imaging / Q000473:pathology; D018281:Cholangiocarcinoma / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000235:genetics*; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed