title: Multifunctional imaging signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer.
abstract: This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer.
  
  
  METHODS
  This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: (18)F-FDG uptake ((18)F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy.
  
  
  RESULTS
  The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%-93.9%), 0% (0%-10.4%), and 90.1% (79.2%-96.0%), respectively. KRAS mutants with high (18)F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low (18)F-FDG SUV(max), high MPP, and high blood flow expressed mcm2 (P = 0.036).
  
  
  CONCLUSIONS
  Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor (18)F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.
authors: University College London/UCLH, London, United Kingdom; and.
authors: Kenneth A
authors: KA
authors: Miles
authors: Balaji
authors: B
authors: Ganeshan
authors: Manuel
authors: M
authors: Rodriguez-Justo
authors: Vicky J
authors: VJ
authors: Goh
authors: Zia
authors: Z
authors: Ziauddin
authors: Alec
authors: A
authors: Engledow
authors: Marie
authors: M
authors: Meagher
authors: Raymondo
authors: R
authors: Endozo
authors: Stuart A
authors: SA
authors: Taylor
authors: Stephen
authors: S
authors: Halligan
authors: Peter J
authors: PJ
authors: Ell
authors: Ashley M
authors: AM
authors: Groves
mesh_terms: D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics*; D003663:Decision Trees; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009154:Mutation; D049268:Positron-Emission Tomography; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D014057:Tomography, X-Ray Computed; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: KRAS protein; colonic neoplasms; comparative study; diagnostic imaging; human