TY - JOUR
T1 - Girdin (GIV) expression as a prognostic marker of recurrence in mismatch repair-proficient stage II colon cancer
AU - Ghosh, Pradipta
AU - Tie, Jeanne
AU - Muranyi, Andrea
AU - Singh, Shalini
AU - Brunhoeber, Patrick
AU - Leith, Katherine
AU - Bowermaster, Rebecca
AU - Liao, Zhiming
AU - Zhu, Yifei
AU - LaFleur, Bonnie
AU - Tran, Ben
AU - Desai, Jayesh
AU - Jones, Ian
AU - Croxford, Matthew
AU - Jover, Rodrigo
AU - Goel, Ajay
AU - Waring, Paul
AU - Hu, Song
AU - Teichgraber, Volker
AU - Rohr, Ulrich Peter
AU - Ridder, Ruediger
AU - Shanmugam, Kandavel
AU - Gibbs, Peter
N1 - Funding Information:
This work was supported by Ventana Medical Systems, Inc., the NIH (R01CA160911 and R01 CA100768, to P. Ghosh; R01 CA72851, CA 181572, and U01 CA187956, to A. Goel), and seed grant from the Moores Cancer Center (P30CA23100, to P. Ghosh) and the Baylor Research Institute (to A. Goel).
Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/7/15
Y1 - 2016/7/15
N2 - Purpose: 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. Experimental Design: 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. Results: 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]. Conclusions: 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.
AB - Purpose: 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. Experimental Design: 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. Results: 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]. Conclusions: 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.
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U2 - 10.1158/1078-0432.CCR-15-2290
DO - 10.1158/1078-0432.CCR-15-2290
M3 - Article
C2 - 27029492
AN - SCOPUS:84978414703
SN - 1078-0432
VL - 22
SP - 3488
EP - 3498
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -