title: Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair-Proficient Stage II Colon Cancer.
abstract: Prognostic markers that identify patients with stage II colon cancers who are at the risk of recurrence are essential to personalize therapy. We evaluated the potential of GIV/Girdin as a predictor of recurrence risk in such patients.
  
  
  
  Expression of full-length GIV was evaluated by IHC using a newly developed mAb together with a mismatch repair (MMR)-specific antibody panel in three stage II colon cancer patient cohorts, that is, a training (n = 192), test (n = 317), and validation (n = 181) cohort, with clinical follow-up data. Recurrence risk stratification models were established in the training cohort of T3, proficient MMR (pMMR) patients without chemotherapy and subsequently validated.
  
  
  
  For T3 pMMR tumors, GIV expression and the presence of lymphovascular invasion (LVI) were the only factors predicting recurrence in both training (GIV: HR, 2.78, P = 0.013; LVI: HR, 2.54, P = 0.025) and combined test and validation (pooled) cohorts (GIV: HR, 1.85, P = 0.019; LVI: HR, 2.52, P = 0.0004). A risk model based on GIV expression and LVI status classified patients into high- or low-risk groups; 3-year recurrence-free survival was significantly lower in the high-risk versus low-risk group across all cohorts [Training: 52.3% vs. 84.8%; HR, 3.74, 95% confidence interval (CI), 1.50-9.32; Test: 85.9% vs. 97.9%, HR, 7.83, 95% CI, 1.03-59.54; validation: 59.4% vs. 84.4%, HR, 3.71, 95% CI, 1.24-11.12].
  
  
  
  GIV expression status predicts recurrence risk in patients with T3 pMMR stage II colon cancer. A risk model combining GIV expression and LVI status information further enhances prediction of recurrence. Further validation studies are warranted before GIV status can be routinely included in patient management algorithms. Clin Cancer Res; 22(14); 3488-98. ©2016 AACR.
authors.affiliation: Departments of Medicine and Cell and Molecular Medicine, University of California, San Diego, California.
authors.forename: Pradipta
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Walter and Eliza Hall Institute, Melbourne, Australia. The Royal Melbourne Hospital, Melbourne, Australia. Western Hospital, Melbourne, Australia.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Tie
authors.affiliation: Ventana Medical Systems, Inc., Tucson, Arizona.
authors.forename: Andrea
authors.initials: A
authors.lastname: Muranyi
authors.affiliation: Ventana Medical Systems, Inc., Tucson, Arizona.
authors.forename: Shalini
authors.initials: S
authors.lastname: Singh
authors.affiliation: Ventana Medical Systems, Inc., Tucson, Arizona.
authors.forename: Patrick
authors.initials: P
authors.lastname: Brunhoeber
authors.affiliation: Ventana Medical Systems, Inc., Tucson, Arizona.
authors.forename: Katherine
authors.initials: K
authors.lastname: Leith
authors.affiliation: Ventana Medical Systems, Inc., Tucson, Arizona.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bowermaster
authors.affiliation: Spring Bioscience, Pleasanton, California.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Spring Bioscience, Pleasanton, California.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Ventana Medical Systems, Inc., Tucson, Arizona.
authors.forename: Bonnie
authors.initials: B
authors.lastname: LaFleur
authors.affiliation: Walter and Eliza Hall Institute, Melbourne, Australia. The Royal Melbourne Hospital, Melbourne, Australia. Western Hospital, Melbourne, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Tran
authors.affiliation: Walter and Eliza Hall Institute, Melbourne, Australia. The Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Desai
authors.affiliation: The Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Jones
authors.affiliation: Western Hospital, Melbourne, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Croxford
authors.affiliation: Department of Gastroenterology, General Hospital University of Alicante, Alicante, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Jover
authors.affiliation: Baylor Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Houston, Texas.
authors.forename: Ajay
authors.initials: A
authors.lastname: Goel
authors.affiliation: Department of Pathology, University of Melbourne, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Waring
authors.affiliation: F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Song
authors.initials: S
authors.lastname: Hu
authors.affiliation: F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Volker
authors.initials: V
authors.lastname: Teichgraber
authors.affiliation: F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Ulrich-Peter
authors.initials: UP
authors.lastname: Rohr
authors.affiliation: Ventana Medical Systems, Inc., Tucson, Arizona.
authors.forename: Ruediger
authors.initials: R
authors.lastname: Ridder
authors.affiliation: Ventana Medical Systems, Inc., Tucson, Arizona. peter.gibbs@mh.org.au kandavel.shanmugam@roche.com.
authors.forename: Kandavel
authors.initials: K
authors.lastname: Shanmugam
authors.affiliation: Walter and Eliza Hall Institute, Melbourne, Australia. The Royal Melbourne Hospital, Melbourne, Australia. Western Hospital, Melbourne, Australia. peter.gibbs@mh.org.au kandavel.shanmugam@roche.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Gibbs
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D053843:DNA Mismatch Repair / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology*; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C502451:CCDC88A protein, human; D008840:Microfilament Proteins; D033921:Vesicular Transport Proteins