Abstract 4918: Is Livin a protagonist of mucinous adenocarcinoma histology in colorectal cancer

The mechanism of cancer resistance to chemotherapy regimen remains uncertain. Colorectal mucinous adenocarcinoma is one of the distinct histological subtypes of the disease implicated in chemotherapeutic resistance associated with nodal and peritoneal metastases and worse disease-free survival as an index of poor prognosis. One of the important acquired capabilities used by the cancer cells to resist anticancer therapies is evasion of apoptosis possibly via inhibitor of apoptosis proteins for which Livin is one. This protein contains baculoviral IAP repeat domains in addition to a RING finger, a protein-protein motif important for binding and inhibition of active caspases that interfere with intrinsic and/or extrinsic pathway and the ensuing blockade of apoptosis. Thus, understanding the molecular events on how cancer cells of mucinous histology evade apoptotic death may provide a novel paradigm for a molecular targeted therapy in the management of colorectal mucinous adenocarcinoma. In this study, the expression pattern and prognostic value of IAP family protein, Livin, in colorectal cancer patients with mucinous histology pre and post-chemotherapy regimen was investigated. Tissue sections from advanced stage colorectal cancer patients who were treated or untreated with neo-adjuvant FOLFOX chemotherapy before curative resection were included in this study. The tissue sections were grouped according to colorectal adenocarcinomas showing mucinous histology and non-mucinous component. Histological study including Haematoxylin and Eosin, and immunohistochemistry for Anti-Livin and DNA mismatched repair proteins were carried out. Immunofluorescence study was performed to clarify the expression pattern of the protein using Anti-Livin antibody. Protein expression quantification study was also used. Results show significant cytoplasmic localisation and expression of Livin protein in the colorectal cancer cells. The Livin protein expression was found to be increased by more than a one-fold post-chemotherapy treatment when compared with pre-chemotherapy treated patients with mucinous histology of colorectal cancer. Younger patients were found to have a greater probability of colorectal mucinous adenocarcinoma diagnosis and worse prognosis. Our findings show that Livin-induced inhibition of apoptosis activity can be a target for novel approaches to treatment and prevention of chemotherapy associated drug resistance in mucinous histology colorectal cancer since Livin