Nanocytology vs. Immunohistochemistry of Intestinal Colonocytes to Assess the Risk of Colon Cancer based on Field Cancerization - A Preliminary Report

The ability to define malignancy in its earliest stages of development is an essential part of any program aimed at attempting to cure the malignant condition. In terms of colon cancer various approaches have been employed to define the transformation of colonocytes as they progress to the fully malignant phenotype. Approaches ranging from nanocytology to mass spectroscopy have been utilized with limited success. Our group at Precision Biologics has been able to define three distinct immunogenic proteins, most oncofetal in origin, which are expressed to various degrees in colon cancer and are essentially absent from normal colon tissue. Monoclonal antibodies (mAbs) have been developed against these tumor associated antigens (TAA), which is NPC-1, 31.1 and 16C3. Each, have shown significant ADCC in the presence of the tumor cells grown in culture. Studies were performed to clarify at what stage in the development of the colon cancer do such TAA proteins begin to be expressed. Utilizing Immunohistochemistry (IHC) with the mAbs targeting the TAA's, we have been able to demonstrate that such antigens appear in the cytoplasm as early as 6 or more months prior to the phenotypic appearance of malignancy utilizing H&E staining. Kits containing these colon Ca monoclonals from our lab, as well as positive and negative controls have been produced for use in the operating room to examine colonocytes at the margin of resection following colectomy; this in order to assure that transforming cells are not incorporated into an anastomosis. We have also been able to demonstrate that premalignant cells as well as those cells present in a fully malignant lesion do shed their antigens into the lumen of the bowel. As such, we have been able to show that a simple “office” stool ELISA can predict with a high degree of accuracy whether a premalignant polypoid lesion, a fully malignant adenocarcinoma or a totally normal colon free of any neoplastic process is present and thus decide on the need for or not, of performing colonoscopy.