Histopathologic and Immunohistochemical Features of Tissue Adherent to the Electr

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DESCRIPTION (provided by applicant): Radiofrequency ablation (RFA) is used for the treatment of non-resectable colon cancer hepatic metastases (CRHM). The technique is designed to cause coagulation necrosis (CN) larger than the target tumor in order to create a 5-10 mm margin to diminish local tumor progression (LTP) and improve outcome. In prior studies we showed that tissue adherent to the electrode after RFA of liver malignancies can be examined by histopathology and immunohistochemistry (IHC) using antibodies to Ki67, a marker of cellular proliferation and Cleave Caspase-3, an apoptotic marker (indicative of CN). Our prior studies demonstrated that when tissue adherent to the electrode was positive for Ki67 a higher LTP rate and shorter time to progression (TTP) was observed. The evaluation of ablated tumor with viability and proliferation markers is extremely important in order to determine whether tumor cells identified on morphologic Hematoxylin & Eosin (H & E) stains are still viable and able to proliferate or if they have been damaged so that they express early apoptotic markers. The goal of this study is to prospectively validate our preliminary results and prove that histopathologic and Immunohistochemical examination of tissue obtained from the ablated tumor can be used as a biomarker of outcome after RFA of CRHM. Our central hypothesis is that the presence of viable tumor cells (Mitotracker (MT) Red or OxPhos antibody (AB) and Ki67 positive tumor cells) increases the probability of incomplete ablation. As a result higher LTP rate and shorter TTP can be expected. To test our central hypothesis we propose the following 3 specific aims: 1. Establish that viable tumor (Ox Phos AB, MT Red and Ki67 positive tumor cells) identified in tissue from the ablated tumor (adherent to the electrode and obtained with needle biopsy) is an independent predictor of LTP and treatment failure after RFA of CRHM. 2. Calculate and Correlate the volume of tumor perfusion and necrosis, using post-RFA dynamic CT imaging, with the presence of viable tumor (MT Red, OxPhos AB and Ki67 positive tumor cells) or coagulation necrosis of the tissue from the ablated tumor (adherent to the electrode and obtained with needle biopsy). 3. Correlate the presence of viable tumor (OxPhos AB, MT Red and Ki67 positive tumor cells) or coagulation necrosis of tissue from the ablated tumor (adherent to the electrode and obtained with needle biopsy) with peripheral blood levels of carcinoembryonic antigen (CEA). According to NCI estimations 100,000 new patients will be diagnosed with colon cancer and almost 50,000 will die from colon and rectal cancer in the US in 2008. As many as 50% of patients with colon cancer, develop hepatic metastases (CRHM). These patients have the highest mortality rate. RFA is a new non-surgical therapy for cancer that has been used with success in the treatment of CRHM. The treatment consists of burning the cancer with a special needle. Unfortunately there is no available method to confirm that at the end of the treatment there is no residual cancer left behind. Our project examines tissue that is found on the RFA electrode or obtained with a biopsy needle from the ablated tumor to determine if there is remaining viable cancer after treatment. Histopathologic and immunohistochemical evaluation of tissue adherent to the electrode or obtained from the ablated tumor by needle biopsy is a novel, minimally invasive, safe and simple test that can be used as a prognostic biomarker of outcome after hepatic RFA. This tissue examination may allow treatment modifications, including repeat RFA that may improve clinical outcome for patients with CRHM. The histopathologic and immunohistochemical findings will also be correlated with post RFA imaging. This may identify and validate specific imaging findings that might be used as surrogate markers of outcome after RFA. The use of biospecimen tests and imaging techniques to measure the impact of interventions and refine treatment to improve outcomes is a priority of the NCI. This information is vital in the treatment of a large population with CRHM and may impact the overall population of cancer patients treated with RFA.