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.