Oncofetal Protein IMP3 as a Predictor of Prognosis in Gastric Adenocarcinoma.
Mikhail Lisovsky, Zhong Jiang, Gregory Y Lauwers. Dartmouth Hitchcock Medical Center, Lebanon, NH, Uzbekistan; UMassMemorial Medical Center, Worcester, MA; Massachusetts General Hospital, Boston
Background: Despite improved long-term survival rates after surgery in association with adjuvant and neo-adjuvant radiation/chemotherapy, gastric adenocarcinoma (GACA) remains a major cause of cancer death worldwide. The aggressiveness of GACA is often difficult to predict based on the pTNM stage alone. One approach to improve stratification of patients for adjuvant and neoadjuvant therapy is to utilize biomarkers that can predict disease outcome. IMP3, an oncofetal protein, is a member of the insulin-like growth factor mRNA binding protein (IMP) family that plays an important role in RNA trafficking and stabilization, cell growth and migration in early embryogenesis. Aberrant overexpression of IMP3 has been associated with malignant transformation and tumor progression in several tumor types. The goal of this study was to evaluate the significance of IMP3 expression for prognosis of GACA.
Design: The study group consisted of 61 resected GACAs, including 32 of diffuse type (mean age 63.9; range 38-82; M:F=15:17) and 29 of intestinal type (mean age 71.1; range 44-92; M:F=20:9). Cytoplasmic IMP3 expression was evaluated immunohistochemically using monoclonal anti-IMP3 antibody (Dako). Immunoreactivity was scored as negative; minimal (staining of 1-10% of tumor cells); moderate (staining of 10-50% of tumor cells) and strong (staining of more than 50% of cells). Overall survival was analyzed using Kaplan-Meier method. The Cox proportional hazards model was used for multivariate analysis.
Results: The results demonstrated a striking difference between tumor types with a significant correlation between survival and IMP3 expression in patients with diffuse GACA. Median overall survival was 22.6 months, (95% CI: 9.55-137.0) in patients with absent/minimal IMP3 staining versus 8.5 months (95% CI: 3.17-14) in patients with moderate/strong IMP3 staining (p=0.006, log-rank test). In multivariate analysis, correcting for the effects of age, sex and pathologic stage, only pathologic stage significantly affected survival (p=0.002). No correlation was observed between survival and IMP3 expression in patients with intestinal GACA. IMP3 staining was negative in 12 normal gastric mucosae serving as control.
Conclusions: Our results suggest that IMP3 may play an important role in refining the progressive potential of GACA and may serve as a helpful prognostic biomarker in evaluating the clinical behavior of diffuse GACA.
Tuesday, March 1, 2011 9:15 AM
Platform Session: Section E, Tuesday Morning