Abstract B33: Osteopontin expression is an independent poor prognostic marker in gastric cancer radically resected. Preliminary report of translational study of ITACA-S (Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach) study.
Authors: Di Bartolomeo Maria , Miceli Rosalba , Pellegrinelli Alessandro , Pietrantonio Filippo , Dotti Fiorella K. , Buzzoni Roberto , Maggi Claudia , Martinetti Antonia , Bajetta Emilio , Mariani Luigi , de Braud Filippo G. 
Published: August 2014

Abstract
Osteopontin is overexpressed in gastric cancer. A correlation of OPN with clinicopathological features and prognosis has been previously shown. The ITACA-S is a randomized study that compares DFS and OS in radically resected gastric cancer patients, that received 5-FU/LV for 9 cycles(control arm) or FOLFIRI regimen for 4 cycles followed by cisplatin/docetaxel for 3 cycles (experimental arm). Inclusion criteria consisted of pN+ or pT3-4 (stage Ib-III). This study showed that the more intensive regimen failed to give any significant benefit versus monotherapy. An ancillary study was carried out for evaluating the prognostic role of different biological factors, prospectively determined on formalin-fixed, paraffin-embedded (FFPE) of primary gastric tumor tissue. The present study, focused on OPN immunohistochemical expression, correlates such biomarker with relapse free survival (RFS) and OS. OPN immunohistochemical expression was scored using a three grades system: negative if no tumor staining was found, positive-focal if &lt; 50% of the tumor and positive-extensive if &gt; 50% of tumor. RFS and OS curves were estimated using the Kaplan-Meier method and compared using the log-rank test. The multivariable analysis were performed using Cox models, in which the association between RFS or OS and OPN was estimated with adjustment for tumor stage, histotype, site and grading. Three-hundred and sixty tumor samples were analyzed, 49% in the control and 51% in the experimental arm. Median follow up was 61 months, 159 patients relapsed and died, 19 who relapsed were alive. The overall number of death was 190. Osteopontin resulted negative in 54 %, positive-focal in 24 % and positive-extended in 22 % of the cases. Six-year RFS was 49.7 %, in negative OPN group; 34% in positive OPN -focal and 22.9% in positive-extended OPN (p=0.0004). The corresponding figures for OS were 53%, 43.2% and 34.2% (p=0.0020). Osteopontin was confirmed as significant prognostic factor also at multivariable analysis (p=0.0011 for RFS and 0.0137 for OS). In patients with IIIb-IIIc stage, RFS was 30% in the negative OPN, 8.4% in the positive-focal and 4.4% in the positive-extended OPN (p=0.0004); OS was 32.4%, 12.8% and 11.4%, respectively (p=0.0013). The subgroup analyses according treatment arm showed that in positive-extended group the RFS was 12.4% in the control arm and 36.7% in the experimental arm (p=0.0751); OS was 28.8% in the control arm and 45.0% in the experimental arm (p=0.1210). No difference was observed between two treatment arms among OPN negative or OPN positive-focal groups. These data provides a definitive role of OPN as poor prognostic factor in patients radically resected. Studies evaluating the efficacy of combined adjuvant treatment in patients with OPN overexpression are warranted.
We thank AIRC (Associazione Italiana Ricerca sul Cancro) for supporting this study.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B33.
Citation Format: Maria Di Bartolomeo, Rosalba Miceli, Alessandro Pellegrinelli, Filippo Pietrantonio, Fiorella K. Dotti, Roberto Buzzoni, Claudia Maggi, Antonia Martinetti, Emilio Bajetta, Luigi Mariani, Filippo G. de Braud. Osteopontin expression is an independent poor prognostic marker in gastric cancer radically resected. Preliminary report of translational study of ITACA-S (Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach) study. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B33.