Histopathologic and Immunohistochemical Features of Tissue Adherent to the Electr

电粘附组织的组织病理学和免疫组织化学特征

• 批准号: 7659816
• 负责人: Constantinos Thasos Sofocleous
• 金额: $ 25.03万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7659816
• 关键词: Ablation; Aftercare; American; Antibodies; Apoptosis; Apoptotic; Appearance; Area; Biological Markers; Burn injury; Cancer Patient; Carcinoembryonic Antigen; Cell Death; Cell Proliferation; Cell Survival; Cells; Cessation of life; Characteristics; Cleaved cell; Clinical; Coagulation Process; Colon; Colon Carcinoma; Colorectal; Colorectal Cancer; Computers; Data; Development; Diagnosis; Disease; Electrodes; Evaluation; Excision; Fluorescence; Genus Cola; Goals; Hematoxylin and Eosin Staining Method; Hepatic; Hepatic Radiofrequency Ablation; Histopathology; Hyperemia; Image; Imaging Techniques; Immunofluorescence Immunologic; Immunohistochemistry; Intervention; Laboratories; Lead; Left; Lesion; Life; Liver; Malignant Neoplasms; Malignant neoplasm of liver; Measures; Metastatic Neoplasm to the Liver; Methodology; Methods; Mitochondria; Modeling; Modification; Morphology; Necrosis; Needle biopsy procedure; Needles; Normal Cell; Operative Surgical Procedures; Outcome; Outcome Study; Oxidative Phosphorylation; Paraffin; Patients; Perfusion; Population; Probability; Procedures; Production; Proliferating; Proliferation Marker; Radial; Radiofrequency Interstitial Ablation; Radiology Specialty; Rectal Cancer; Recurrence; Resectable; Residual Cancers; Risk; Safety; Solid Neoplasm; Specimen; Staining method; Stains; Surgical margins; Surrogate Markers; Techniques; Testing; Time; Tissue Viability; Tissues; Treatment Efficacy; Treatment Failure; Tumor Volume; Validation; alternative treatment; base; cancer cell; cancer therapy; caspase-3; cell fixing; cohort; density; design; follow-up; high risk; imaging modality; improved; minimally invasive; mortality; neoplastic cell; novel; peripheral blood; prognostic; public health relevance; response; success; tumor; tumor progression

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. PUBLIC HEALTH RELEVANCE: Over a100,000 Americans are diagnosed with liver cancer each year and almost 50,000 will die from colon and rectal cancer in the US in 2008. Radiofrequency Ablation (RFA) is a new non-surgical treatment of cancer that has been used with success in the treatment of liver cancers. The treatment consists of burning the cancer with a special needle. Unfortunately there is no method available 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 needle after burning of colon cancer that involves the liver to determine if there is remaining live cancer at the end of the treatment. This information may be used to retreat those patients with evidence of cancer on the needle. This is vital in the treatment of a large population with liver cancers and may impact the overall population of cancer patients treated with RFA.

描述（由申请方提供）：射频消融（RFA）用于治疗不可切除的结肠癌肝转移（CRHM）。该技术旨在引起比靶肿瘤更大的凝固性坏死（CN），以产生5-10 mm的边缘，从而减少局部肿瘤进展（LTP）并改善结局。在之前的研究中，我们表明，可以通过组织病理学和免疫组织化学（IHC）使用Ki 67（细胞增殖标记物）和Cleave Caspase-3（细胞凋亡标记物（指示CN））的抗体检查肝脏恶性肿瘤RFA后粘附到电极上的组织。我们之前的研究表明，当粘附到电极的组织对Ki 67呈阳性时，观察到更高的LTP率和更短的进展时间（TTP）。为了确定在形态学苏木精和伊红（H & E）染色上鉴定的肿瘤细胞是否仍然存活并且能够增殖，或者它们是否已经被损坏使得它们表达早期凋亡标记物，用存活力和增殖标记物评估消融的肿瘤是极其重要的。本研究的目的是前瞻性地验证我们的初步结果，并证明从消融肿瘤中获得的组织的组织病理学和免疫组织化学检查可用作CRHM RFA后结果的生物标志物。我们的中心假设是，活肿瘤细胞（Mitotracker（MT）Red或OxPhos抗体（AB）和Ki 67阳性肿瘤细胞）的存在增加了不完全消融的概率。因此，可以预期更高的LTP率和更短的TTP。为了检验我们的中心假设，我们提出了以下3个具体目标：1。确定在消融肿瘤组织（粘附于电极并通过针吸活检获得）中识别出的存活肿瘤（Ox Phos AB、MT Red和Ki 67阳性肿瘤细胞）是CRHM RFA后LTP和治疗失败的独立预测因子。2.使用RFA后动态CT成像计算肿瘤灌注和坏死体积，并将其与存在的活肿瘤（MT Red、OxPhos AB和Ki 67阳性肿瘤细胞）或消融肿瘤组织的凝固性坏死（粘附在电极上并通过穿刺活检获得）相关联。3.将存活肿瘤（OxPhos AB、MT Red和Ki 67阳性肿瘤细胞）或消融肿瘤组织凝固性坏死（粘附在电极上并通过针吸活检获得）的存在与外周血癌胚抗原（CEA）水平相关联。据NCI估计，2008年美国将有10万新患者被诊断为结肠癌，近5万人将死于结肠癌和直肠癌。多达50%的结肠癌患者发生肝转移（CRHM）。这些患者的死亡率最高。RFA是一种新的非手术治疗癌症的方法，已成功用于治疗CRHM。治疗包括用一种特殊的针烧灼癌症。不幸的是，没有可用的方法来确认在治疗结束时没有残留的癌症。我们的项目检查RFA电极上发现的组织或用活检针从消融的肿瘤中获得的组织，以确定治疗后是否有剩余的存活癌症。对粘附在电极上的组织或通过针吸活检从消融肿瘤中获得的组织进行组织学和免疫组织化学评价是一种新型、微创、安全和简单的检测，可用作肝脏RFA后结局的预后生物标志物。这种组织检查可能允许治疗调整，包括重复RFA，这可能会改善CRHM患者的临床结局。组织病理学和免疫组织化学结果也将与RFA后成像相关。这可以识别和验证特定的成像结果，这些结果可能用作RFA后结局的替代标志物。使用生物样本测试和成像技术来测量干预措施的影响并改进治疗以改善结果是NCI的优先事项。这一信息对于CRHM大人群的治疗至关重要，并可能影响RFA治疗的癌症患者的总体人群。公共卫生相关性：每年有超过10万的美国人被诊断出患有肝癌，2008年美国将有近5万人死于结肠癌和直肠癌。射频消融（RFA）是一种新型的非手术治疗癌症的方法，已成功用于治疗肝癌。治疗包括用一种特殊的针烧灼癌症。不幸的是，没有方法可以证实在治疗结束时没有残留的癌症。我们的项目检查了在涉及肝脏的结肠癌燃烧后在针上发现的组织，以确定在治疗结束时是否有剩余的肝癌。这些信息可用于撤回那些针上有癌症证据的患者。这对于治疗大量肝癌患者至关重要，并可能影响接受RFA治疗的癌症患者的总体人群。