Strong IMP3 Expression Is Associated with Reduced E-Cadherin Level and Decreased Survival in Rectal Adenocarcinoma Patients after Neoadjuvant Therapy
Xiaofang Yang, Ediz F Cosar, Lloyd Hutchinson, Zhong Jiang, Karen Dresser, Hwajeong Lee. UMass Memorial Medical Center, Worcester, MA; Albany Medical College, Albany, NY
Background: Preoperative neoadjuvant therapy has become a standard management for locally advanced rectal adenocarcinoma. No promising biomarkers to predict outcomes following neoadjuvant therapy and surgery have been found. IMP3, an oncofetal protein, is a member of the insulin-like growth factor-II mRNA-binding protein family and has been used as a biomarker for both epithelial and mesenchymal malignancies. E-cadherin, an epithelial cell-cell adhesion protein, is often lost in advanced cancers and may play a role in epithelial-to-mesenchymal transition. In this study, we investigated the expression patterns of IMP3 and E-cadherin in tumor cells and their potential association with prognosis in rectal adenocarcinomas resected after neoadjuvant therapy.
Design: Rectal adenocarcinomas resected after neoadjuvant therapy at our institution from 2002 to 2010 with at least 2 years of follow up were retrieved. IMP3 and E-cadherin immunohistochemical stains were performed on representative paraffin-embedded tumor tissue blocks. IMP3 and E-cadherin staining were quantitatively scored as 3+, 2+, 1+, and negative with a cutoff of >40%, 16-39%, 5-15%, and <5% of tumor cells staining, respectively. Survival data were obtained from the Tumor Registry Office.
Results: Thirty four cases were available, with 17 macroscopic and 17 microscopic residual tumors. Twenty were male and 14 were female with the median age at resection of 58 years. Two-year survival rate was 66% in macroscopic and 100% in microscopic tumor cases. IMP3 showed 3+, 2+, 1+ and negative staining in 4, 2, 2, and 7 macroscopic tumor cases, respectively. Majority of the macroscopic tumor cases showed 3+ positivity for E-cadherin. All four 1+ E-cadherin positive cases showed 3+ IMP3 staining. The 4-year overall survival rate was 88% in negative and 1+ IMP3 positive cases and 62% in 2+ and 3+ IMP3 positive cases. Scarcity of the tumor cells and exhaustion of the blocks precluded a reliable comparative assessment of the stains in the microscopic tumor cases and 2 macroscopic tumor cases.
Conclusions: Our preliminary data suggest that strong IMP3 expression in residual tumor cells is associated with reduced E-cadherin level and decreased 4-year survival in treated rectal adenocarcinomas with macroscopic residual disease. Opposing expression pattern of IMP3 and E-cadherin in tumor cells may be a novel dual biomarker in predicting outcomes after neoadjuvant therapy.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 142, Tuesday Afternoon