- Email: [email protected]
Giv As a Novel Prognostic Marker in Stage Ii Colon Cancer
Annals of Oncology 25 (Supplement 4): iv167–iv209, 2014 doi:10.1093/annonc/mdu333.71
gastrointestinal tumours, colorectal GIV AS A NOVEL PROGNOSTIC MARKER IN STAGE II COLON CANCER
Aim: There is an evident unmet need to better define recurrence risk for patients with stage II colon cancer (CC), particularly those with mismatch repair proficient ( pMMR) tumors, to determine the subgroup of patients that may benefit from adjuvant chemotherapy. GIV/Girdin is a novel metastasis associated protein that triggers tumor cell invasion by enhancing PI3K/AKT signaling downstream of multiple oncogenic receptors. We explored the potential of GIV as a prognostic marker in stage II CC. Methods: A MMR antibody panel and a GIV specific antibody were developed by Ventana and evaluated by immunohistochemistry (IHC) on a cohort of stage II CC from Melbourne (n = 192), enriched for patients with recurrent disease (n = 44, 25%). Log rank test was used to assess the association of GIV IHC expression status with the recurrence risk. Evaluation of alternative GIV scoring algorithms, combining staining intensity and percent staining, and statistical predictive modeling including the analysis of distant recurrence free survival (DRFS) was undertaken for the chemo-naïve cases, stratified by MMR and AJCC tumor (T) status. The association between GIV IHC status and standard histopathologic criteria was also assessed. Results: The distribution of deficient MMR (dMMR) vs pMMR cases were 20.8% and 79.2%, respectively. Within the chemo-naïve population (n = 103), expected associations between pathologic features and DRFS were observed, including pMMR vs dMMR (HR 4.12, p = 0.052), T4 vs T3 (HR 2.39, p = 0.055) and lymphovascular invasion (LVI) vs no LVI (HR 2.62, p = 0.021). GIV positivity, defined as >10% of tumor cells stained or any staining of 3+ intensity, was present in 45 (44.0%) of pMMR chemo-naïve cases. For T3 pMMR chemo-naïve cases (n = 91), GIV positivity was associated with significantly reduced DRFS (HR 2.49, p = 0.022). Adding LVI as an additional parameter to the algorithm for this group increased the HR to 4.74 (95% CI 1.90-11.85). Conclusions: GIV IHC expression status has been found to be associated with T3 disease, pMMR, and DRFS in an initial cohort of stage II CC. This exploratory diagnostic algorithm currently undergoes validation in two independent clinical stage II CC cohorts, with promising preliminary data. Disclosure: P. Waring: received research grant funding from F. Hoffmann-La Roche; B. Lafleur, A. Muranyi, S. Singh and P. Brunhoeber: Employee of Ventana Medical Systems, Inc., a member of the Roche Group; S. Hu, V. Teichgräber, U. Rohr, R. Ridder:. and K. Shanmugam: Employee of F. Hoffmann-La Roche Ltd. All other authors have declared no conflicts of interest.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv195/2241346 by guest on 24 October 2019
P. Gibbs1, P. Ghosh2, P. Waring3, B. Lafleur4, A. Muranyi4, S. Singh4, P. Brunhoeber4, J. Tie1, B. Tran1, J. Desai1, R. Martinez5, K. Janssen6, A. Goel7, S. Hu8, V. Teichgräber8, U. Rohr8, R. Ridder4, K. Shanmugam4 1 Medical Oncology, Walter and Eliza Hall Institute, Parkville, VIC, AUSTRALIA 2 Department of Medicine, Gastroenterology, University of California, San Diego, La Jolla, CA, USA 3 Department of Pathology, University of Melbourne, Melbourne, ACT, AUSTRALIA 4 Research, Ventana Medical Systems, Inc., Tucson, AZ, USA 5 Department of Gastroenterology, University of Alicante General Hospital, Alicante, SPAIN 6 Department of Surgery, Technical University Munich, München, GERMANY 7 Baylor Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Huston, TX, USA 8 Diagnostics Division, F. Hoffmann-La Roche Ltd, Basel, SWITZERLAND
abstracts
569P
gastrointestinal tumours, colorectal GIV AS A NOVEL PROGNOSTIC MARKER IN STAGE II COLON CANCER
Aim: There is an evident unmet need to better define recurrence risk for patients with stage II colon cancer (CC), particularly those with mismatch repair proficient ( pMMR) tumors, to determine the subgroup of patients that may benefit from adjuvant chemotherapy. GIV/Girdin is a novel metastasis associated protein that triggers tumor cell invasion by enhancing PI3K/AKT signaling downstream of multiple oncogenic receptors. We explored the potential of GIV as a prognostic marker in stage II CC. Methods: A MMR antibody panel and a GIV specific antibody were developed by Ventana and evaluated by immunohistochemistry (IHC) on a cohort of stage II CC from Melbourne (n = 192), enriched for patients with recurrent disease (n = 44, 25%). Log rank test was used to assess the association of GIV IHC expression status with the recurrence risk. Evaluation of alternative GIV scoring algorithms, combining staining intensity and percent staining, and statistical predictive modeling including the analysis of distant recurrence free survival (DRFS) was undertaken for the chemo-naïve cases, stratified by MMR and AJCC tumor (T) status. The association between GIV IHC status and standard histopathologic criteria was also assessed. Results: The distribution of deficient MMR (dMMR) vs pMMR cases were 20.8% and 79.2%, respectively. Within the chemo-naïve population (n = 103), expected associations between pathologic features and DRFS were observed, including pMMR vs dMMR (HR 4.12, p = 0.052), T4 vs T3 (HR 2.39, p = 0.055) and lymphovascular invasion (LVI) vs no LVI (HR 2.62, p = 0.021). GIV positivity, defined as >10% of tumor cells stained or any staining of 3+ intensity, was present in 45 (44.0%) of pMMR chemo-naïve cases. For T3 pMMR chemo-naïve cases (n = 91), GIV positivity was associated with significantly reduced DRFS (HR 2.49, p = 0.022). Adding LVI as an additional parameter to the algorithm for this group increased the HR to 4.74 (95% CI 1.90-11.85). Conclusions: GIV IHC expression status has been found to be associated with T3 disease, pMMR, and DRFS in an initial cohort of stage II CC. This exploratory diagnostic algorithm currently undergoes validation in two independent clinical stage II CC cohorts, with promising preliminary data. Disclosure: P. Waring: received research grant funding from F. Hoffmann-La Roche; B. Lafleur, A. Muranyi, S. Singh and P. Brunhoeber: Employee of Ventana Medical Systems, Inc., a member of the Roche Group; S. Hu, V. Teichgräber, U. Rohr, R. Ridder:. and K. Shanmugam: Employee of F. Hoffmann-La Roche Ltd. All other authors have declared no conflicts of interest.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv195/2241346 by guest on 24 October 2019
P. Gibbs1, P. Ghosh2, P. Waring3, B. Lafleur4, A. Muranyi4, S. Singh4, P. Brunhoeber4, J. Tie1, B. Tran1, J. Desai1, R. Martinez5, K. Janssen6, A. Goel7, S. Hu8, V. Teichgräber8, U. Rohr8, R. Ridder4, K. Shanmugam4 1 Medical Oncology, Walter and Eliza Hall Institute, Parkville, VIC, AUSTRALIA 2 Department of Medicine, Gastroenterology, University of California, San Diego, La Jolla, CA, USA 3 Department of Pathology, University of Melbourne, Melbourne, ACT, AUSTRALIA 4 Research, Ventana Medical Systems, Inc., Tucson, AZ, USA 5 Department of Gastroenterology, University of Alicante General Hospital, Alicante, SPAIN 6 Department of Surgery, Technical University Munich, München, GERMANY 7 Baylor Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Huston, TX, USA 8 Diagnostics Division, F. Hoffmann-La Roche Ltd, Basel, SWITZERLAND
abstracts
569P