Expression of Insulin-Like Growth Factor II mRNA-Binding Protein 3 (IMP3) in Human Esophageal Adenocarcinoma and Its Precursor Lesions
W Feng, CD Truong, J Zhai, Z Zhou, D Tan. The University of Texas MD Anderson Cancer Center, Houston, TX; The Methodist Hospital, Houston, TX; The University of Rochester, Rochester, NY
Background: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein highly expressed in fetal tissue and malignant tumors such as endometrial carcinomas, renal cell carcinomas and melanoma, but only rarely within adult benign tissues. The prevalence and significance of IMP3 in esophageal adenocarcinoma (EAC) and its precursor lesions including distinctive type Barrett's mucosa (intestinal metaplasia, BM), and dysplasia are largely unknown.
Design: Samples from 155 cases of esophageal adenocarcinoma, 21 cases of esophageal columnar dysplasia (12 high grade dysplasia and 9 low grade dysplasia cases), 31 cases of BM without dysplasia and 122 cases of non-neoplastic esophageal mucosa without dysplasia or BM within formalin-fixed paraffin-embedded tissue microarray blocks were examined. Cases with preoperative treatment were excluded. Tissue microarrays were stained with mouse monoclonal anti-IMP3 antibody (Dako, 1:80) with adequate positive and negative controls. The percent (0-100%) and intensity (1-3+) of positive cytoplamic and/or membranous IMP3 staining cells were determined.
Results: A subset of EAC cases (103, 66%) showed positive cytoplasmic and membranous IMP3 staining. Sixty percent of poorly differentiated EAC showed strong IMP3 staining (2-3+) compared to well and moderately differentiated EAC (48% and 45% respectively). In addition poorly differentiated EAC showed statistically significant higher IMP3 expression compared to well differentiated EAC (p<0.005), Twenty-four percent of dysplasia cases were positive for IMP3. Four low grade dysplasia case showed positive (1+ in <15% of lesional cells) IMP3 staining and 1 high grade dysplasia cases showed positive diffuse 2+ IMP3 staining. In contrast, only 1 BM case showed positive diffuse 2+ IMP3 staining and no IMP3 staining was observed in any of the non-neoplastic esophageal mucosa without dysplasia or BM.
Conclusions: This study shows that IMP3 is overexpressed in esophageal adenocarcinomas, and is expressed significantly in lower frequency of pre-neoplastic lesions and are negative in non-preneoplastic esophageal mucosa. Furthermore, statistically significant differences in level of IMP3 expression between well differentiated and poorly differentiated EACs, suggest that IMP3 over-expression may have potential prognostic implications in EAC.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 94, Wednesday Afternoon