Cholangiocarcinoma: Correlation between molecular profiling and imaging phenotypes Journal Article


Authors: Sadot, E.; Simpson, A. L.; Do, R. K. G.; Gonen, M.; Shia, J.; Allen, P. J.; D'Angelica, M. I.; DeMatteo, R. P.; Kingham, T. P.; Jarnagin, W. R.
Article Title: Cholangiocarcinoma: Correlation between molecular profiling and imaging phenotypes
Abstract: Purpose 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. Conclusion Quantitative imaging phenotypes, as defined by texture analysis, correlated with expression of specific markers of hypoxia, regardless of conventional imaging features. Copyright: © 2015 Sadot et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: vasculotropin; adult; clinical article; controlled study; protein expression; aged; overall survival; antigen expression; progression free survival; computer assisted tomography; image analysis; epidermal growth factor receptor; retrospective study; protein p53; carbonate dehydratase ix; contrast enhancement; image quality; iohexol; bile duct carcinoma; image processing; hypoxia inducible factor 1alpha; cd24 antigen; predictive value; immunochemistry; protein mdm2; glucose transporter 1; human; male; female; article; multidrug resistance associated protein 1
Journal Title: PLoS ONE
Volume: 10
Issue: 7
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2015-07-24
Start Page: e0132953
Language: English
DOI: 10.1371/journal.pone.0132953
PROVIDER: scopus
PMCID: PMC4514866
PUBMED: 26207380
DOI/URL:
Notes: Export Date: 2 October 2015 -- Source: Scopus
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MSK Authors
  1. Ronald P DeMatteo
    637 DeMatteo
  2. Mithat Gonen
    1029 Gonen
  3. Jinru Shia
    720 Shia
  4. Peter Allen
    501 Allen
  5. William R Jarnagin
    903 Jarnagin
  6. Kinh Gian Do
    257 Do
  7. T Peter Kingham
    609 Kingham
  8. Amber L Simpson
    64 Simpson
  9. Eran Sadot
    38 Sadot