Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair-Proficient Stage II Colon Cancer
Por:
Ghosh, P, Tie, J, Muranyi, A, Singh, S, Brunhoeber, P, Leith, K, Bowermaster, R, Liao, Z, Zhu, Y, LaFleur, B, Tran, B, Desai, J, Jones, I, Croxford, M, Jover R, Goel, A, Waring, P, Hu, S, Teichgraber, V, Rohr, U, Ridder, R, Shanmugam, K and Gibbs, P
Publicada:
15 jul 2016
Resumen:
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 T3p MMR 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. = 2016 AACR.
Filiaciones:
Ghosh, P:
Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA
Univ Calif San Diego, Dept Cell & Mol Biol, San Diego, CA 92103 USA
Tie, J:
Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia
Royal Melbourne Hosp, Grattan St, Melbourne, Vic 3050, Australia
Western Hosp, Melbourne, Vic, Australia
Muranyi, A:
Ventana Med Syst Inc, 1910 E Innovat Pk Dr, Tucson, AZ 85755 USA
Singh, S:
Ventana Med Syst Inc, 1910 E Innovat Pk Dr, Tucson, AZ 85755 USA
Brunhoeber, P:
Ventana Med Syst Inc, 1910 E Innovat Pk Dr, Tucson, AZ 85755 USA
Leith, K:
Ventana Med Syst Inc, 1910 E Innovat Pk Dr, Tucson, AZ 85755 USA
Bowermaster, R:
Ventana Med Syst Inc, 1910 E Innovat Pk Dr, Tucson, AZ 85755 USA
Liao, Z:
Spring Biosci, Pleasanton, CA USA
Zhu, Y:
Spring Biosci, Pleasanton, CA USA
LaFleur, B:
Ventana Med Syst Inc, 1910 E Innovat Pk Dr, Tucson, AZ 85755 USA
Tran, B:
Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia
Royal Melbourne Hosp, Grattan St, Melbourne, Vic 3050, Australia
Western Hosp, Melbourne, Vic, Australia
Desai, J:
Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia
Royal Melbourne Hosp, Grattan St, Melbourne, Vic 3050, Australia
Jones, I:
Royal Melbourne Hosp, Grattan St, Melbourne, Vic 3050, Australia
Croxford, M:
Western Hosp, Melbourne, Vic, Australia
Jover R:
Hosp Gen Univ Alicante, Dept Gastroenterol, Alicante, Spain
Goel, A:
Baylor Univ, Med Ctr, Baylor Res Inst, Houston, TX 77030 USA
Baylor Univ, Med Ctr, Charles A Sammons Canc Ctr, Houston, TX 77030 USA
Waring, P:
Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia
Hu, S:
F Hoffmann La Roche & Cie AG, Basel, Switzerland
Teichgraber, V:
F Hoffmann La Roche & Cie AG, Basel, Switzerland
Rohr, U:
F Hoffmann La Roche & Cie AG, Basel, Switzerland
Ridder, R:
Ventana Med Syst Inc, 1910 E Innovat Pk Dr, Tucson, AZ 85755 USA
Shanmugam, K:
Ventana Med Syst Inc, 1910 E Innovat Pk Dr, Tucson, AZ 85755 USA
Gibbs, P:
Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia
Royal Melbourne Hosp, Grattan St, Melbourne, Vic 3050, Australia
Western Hosp, Melbourne, Vic, Australia
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