Eirini Pectasides1, Ioannis Chatzidakis2, Vassiliki Kotoula3,4, Georgia-Angeliki Koliou5, Kyriaki Papadopoulou4, Eleni Giannoulatou6,7, Vasilios G Giannouzakos8, Mattheos Bobos4, Christos Papavasileiou9, Sofia Chrisafi4, Aikaterini Florou2, Dimitrios Pectasides2, George Fountzilas4,10,11. 1. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, U.S.A. eirini_pectasides@dfci.harvard.edu hecogoff@otenet.gr. 2. Second Department of Internal Medicine, Propaedeutic, Oncology Section, National and Kapodistrian University of Athens, University General Hospital Attikon, Athens, Greece. 3. Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece. 4. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece. 5. Section of Biostatistics, Hellenic Cooperative Oncology Group, Athens, Greece. 6. Bioinformatics and Systems Medicine Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia. 7. The University of New South Wales, Kensington, NSW, Australia. 8. Department of Radiation Therapy, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece. 9. Surgical Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece. 10. Aristotle University of Thessaloniki, Thessaloniki, Greece. 11. German Oncology Center, Limassol, Cyprus.
Abstract
BACKGROUND/AIM: Early-stage gastric cancer has a high risk of recurrence, despite trimodality therapy with surgery, chemotherapy and radiation. To improve patient selection for adjuvant chemoradiotherapy, we evaluated the prognostic significance of immunohistochemical and genetic biomarkers in patients with resected gastric adenocarcinoma. PATIENTS AND METHODS: Tumors from 119 patients were subjected to immunohistochemistry for 12 protein biomarkers, as well as next-generation sequencing. Clinical and biomarker data were available for 91 patients. RESULTS: EBV-positive tumors and tumors with mutations had higher intratumoral CD8 tumor-infiltrating lymphocyte density (p=0.009 and p=0.017, respectively). PIK3CA mutations were correlated with VEGFA overexpression (p=0.042), while KRAS mutations and HER2 expression were mutually exclusive (p=0.036). PTEN expression univariately confirmed longer overall survival (HR=0.27; p=0.046), while there was a trend between the presence of KRAS mutations and inferior disease-free and overall survival. CONCLUSION: PTEN protein expression and KRAS mutations may predict disease outcome in early-stage gastric cancer. These results need to be further validated in larger cohorts. Copyright
BACKGROUND/AIM: Early-stage gastric cancer has a high risk of recurrence, despite trimodality therapy with surgery, chemotherapy and radiation. To improve patient selection for adjuvant chemoradiotherapy, we evaluated the prognostic significance of immunohistochemical and genetic biomarkers in patients with resected gastric adenocarcinoma. PATIENTS AND METHODS: Tumors from 119 patients were subjected to immunohistochemistry for 12 protein biomarkers, as well as next-generation sequencing. Clinical and biomarker data were available for 91 patients. RESULTS: EBV-positive tumors and tumors with mutations had higher intratumoral CD8tumor-infiltrating lymphocyte density (p=0.009 and p=0.017, respectively). PIK3CA mutations were correlated with VEGFA overexpression (p=0.042), while KRAS mutations and HER2 expression were mutually exclusive (p=0.036). PTEN expression univariately confirmed longer overall survival (HR=0.27; p=0.046), while there was a trend between the presence of KRAS mutations and inferior disease-free and overall survival. CONCLUSION:PTEN protein expression and KRAS mutations may predict disease outcome in early-stage gastric cancer. These results need to be further validated in larger cohorts. Copyright
Authors: Eirini Pectasides; Matthew D Stachler; Sarah Derks; Yang Liu; Steven Maron; Adam J Bass; Daniel V Catenacci; Mirazul Islam; Lindsay Alpert; Heewon Kwak; Hedy Kindler; Blase Polite; Manish R Sharma; Kenisha Allen; Emily O'Day; Samantha Lomnicki; Melissa Maranto; Rajani Kanteti; Carrie Fitzpatrick; Christopher Weber; Namrata Setia; Shu-Yuan Xiao; John Hart; Rebecca J Nagy; Kyoung-Mee Kim; Min-Gew Choi; Byung-Hoon Min; Katie S Nason; Lea O'Keefe; Masayuki Watanabe; Hideo Baba; Rick Lanman; Agoston T Agoston; David J Oh; Andrew Dunford; Aaron R Thorner; Matthew D Ducar; Bruce M Wollison; Haley A Coleman; Yuan Ji; Mitchell C Posner; Kevin Roggin; Kiran Turaga; Paul Chang; Kyle Hogarth; Uzma Siddiqui; Andres Gelrud; Gavin Ha; Samuel S Freeman; Justin Rhoades; Sarah Reed; Greg Gydush; Denisse Rotem; Jon Davison; Yu Imamura; Viktor Adalsteinsson; Jeeyun Lee Journal: Cancer Discov Date: 2017-10-04 Impact factor: 39.397
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