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SSAT 51st Annual Meeting Abstracts

Back to Program | 2010 Program and Abstracts Overview | 2010 Posters


Expression of the Cancer Testis Antigen Igf2bp3 (Imp3) in Colorectal Cancers; Imp3 Holds Promise As a Specific Immunotherapy Target
C. M. Shantha Kumara H*1, Otavia L. Caballero2, Su Tao3, Aqeel Ahmed3, Vesna Cekic1, Sacha Gnjatic2, Andrew J. Simpson4, Carlos Cordon-Cardo3, Richard L. Whelan1
1Colon and Rectal Surgery,Department of Surgery, St Luke Roosevelt Hospital, New York, NY; 2Ludwig Institute for Cancer Research Ltd, New York Branch of Human Cancer Immunology at Memorial Sloan-Kettering, New York, NY; 3Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center,Columbia University, New York, NY; 4Ludwig Institute for Cancer Research, New York, NY

Introduction: IGF2BP3 (IMP3) is a member of the insulin-like growth factor mRNA binding protein (IMP) family that plays a role in RNA trafficking and stabilization as well as cell growth and migration early in embryogenesis. IMP3 is undetectable in adult human tissues yet is found in the testes, thus, it is considered a cancer testis (CT) protein. Several other CT proteins have proven to be reasonable vaccine targets.Although, increased IMP3 expression has been noted in cancers of the pancreas, kidney, ovary, and liver, expression in colorectal cancer (CRC) has not been studied. This study's aim was to assess IMP3 expression in CRC and, thus, determine if IMP3 has potential as a vaccine target.Method: CRC patients for whom adequate tumor and normal tissue samples were available from an IRB approved tissue and data bank were enrolled. Demographic, clinical, pathologic and short term outcome data were collected prospectively. Tumor samples were OCT embedded and stored at -80C until analysis. Total RNA was isolated and purified from tissue samples and cDNA synthesized. IMP3 expression was analyzed by quantitative PCR(QPCR) using the SYBR Green platform. Comparative quantitative analysis was performed based on the delta-delta Ct method with GAPDH as internal control. Tumor and testes IMP3 expression levels were determined and compared; tumors with levels 0.1% or more than the testes were considered positive. Immunohistochemistry (IHC) of tumor and normal tissue for IMP3 expression was also performed. Results: A total of 78 paired CRC and normal tissue specimens (36 M/ 42 F, age 67+/-14.5) were assessed (88% colon, 12% rectal; pathologic stage 2, 44; stage 3, 34). In 65% of tumors the IMP3 expression levels were at least 0.1% of the testes level and, also, the tumor to normal tissue IMP3 expression ratio was greater than 1. IHC was carried out on 46 paired tumor and normal tissue sections; IMP3 staining was noted in 50% of the tumor sections (1+ to 3+ intensity) and in 5% of the normal tissue sections (1+ to 2+). Non-significant increases in IMP3 expression levels were noted in the Stage 3 and node positive tumors. The median tumor expression level was higher in women (p=0.036).Discussion: The majority of CRC tumors expressed IMP3 as judged by RT-PCR and IHC. This is in distinction to the low CRC expression levels noted for other CT proteins in previous studies. A larger and more diverse group of tumors (Stage 1-4) needs to be assessed to determine if IMP3 expression correlates with T, N, or final tumor stage. Assessment of blood for anti-IMP3 antibodies and IMP3 protein is also needed. IMP3 holds some promise as a vaccine target.


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