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: 8128606
• 负责人: Constantinos Thasos Sofocleous
• 金额: $ 20.23万
• 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 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8128606
• 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 Carcinoma; Colorectal; Colorectal Cancer; Computers; Data; Development; Diagnosis; Disease; Electrodes; Evaluation; Excision; Fluorescence; Goals; Health; 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; 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; 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.

描述（由申请人提供）：射频消融（RFA）用于治疗不可切除的结肠癌肝转移（CRHM）。该技术旨在使凝固性坏死（CN）大于目标肿瘤，以创造5-10毫米的边缘，以减少局部肿瘤进展（LTP）并改善预后。在之前的研究中，我们发现肝脏恶性肿瘤射频消融后附着在电极上的组织可以通过组织病理学和免疫组化（IHC）检测，使用Ki67抗体（细胞增殖标志物）和Cleave Caspase-3抗体（凋亡标志物）（CN指示物）。我们之前的研究表明，当附着在电极上的组织Ki67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Hematoxylin & Eosin （H & E）染色上鉴定的肿瘤细胞是否仍然存活并能够增殖，或者它们是否已经受损，从而表达早期凋亡标志物，对消融肿瘤的生存能力和增殖标志物进行评估是非常重要的。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病理学和免疫组织化学检查可以作为CRHM RFA后预后的生物标志物。我们的中心假设是活的肿瘤细胞(Mitotracker （MT) Red或OxPhos抗体（AB）和Ki67阳性肿瘤细胞）的存在增加了不完全消融的可能性。因此，可以预期更高的LTP率和更短的TTP。为了验证我们的中心假设，我们提出以下3个具体目标：1。确定在消融肿瘤组织（附着在电极上并通过针活检获得）中发现的活肿瘤（Ox Phos AB， MT Red和Ki67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的体积，并将其与存活肿瘤（MT Red， OxPhos AB和Ki67阳性肿瘤细胞）或消融肿瘤组织（粘附在电极上并通过针活检获得）的存在相关联。3. 将活肿瘤（OxPhos AB， MT Red和Ki67阳性肿瘤细胞）或消融肿瘤组织（粘附在电极上并通过针活检获得）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10万名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）。这些病人的死亡率最高。RFA是一种新的非手术治疗癌症的方法，已成功用于治疗CRHM。治疗包括用一根特殊的针灼烧癌细胞。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。我们的项目检查在射频消融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，以确定治疗后是否存在剩余的可存活的癌症。组织病理学和免疫组织化学评估粘附在电极上的组织或通过穿刺活检从消融的肿瘤中获得的组织是一种新颖、微创、安全、简单的测试，可作为肝RFA后预后的生物标志物。该组织检查可能允许治疗修改，包括重复RFA，可能改善CRHM患者的临床结果。组织病理学和免疫组织化学结果也将与RFA后成像相关。这可以识别和验证可能用作RFA后预后替代标记的特定影像学发现。使用生物标本测试和成像技术来衡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。这一信息对大量CRHM患者的治疗至关重要，并可能影响RFA治疗的总体癌症患者。

项目成果

Ki-67 is a prognostic biomarker of survival after radiofrequency ablation of liver malignancies.

• DOI: 10.1245/s10434-012-2461-9
• 发表时间: 2012-12
• 期刊: Annals of surgical oncology
• 影响因子: 3.7
• 作者: Sofocleous CT;Garg S;Petrovic LM;Gonen M;Petre EN;Klimstra DS;Solomon SB;Brown KT;Brody LA;Covey AM;Dematteo RP;Schwartz L;Kemeny NE
• 通讯作者: Kemeny NE

CT-guided radiofrequency ablation as a salvage treatment of colorectal cancer hepatic metastases developing after hepatectomy.

• DOI: 10.1016/j.jvir.2011.01.451
• 发表时间: 2011-06
• 期刊: JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
• 影响因子: 2.9
• 作者: Sofocleous, Constantinos T.;Petre, Elena N.;Gonen, Mithat;Brown, Karen T.;Solomon, Stephen B.;Covey, Anne M.;Alago, William;Brody, Lynn A.;Thornton, Raymond H.;D'Angelica, Michael;Fong, Yuman;Kemeny, Nancy E.
• 通讯作者: Kemeny, Nancy E.

Immunofluorescence Assay of Ablated Colorectal Liver Metastases: The Frozen Section of Image-Guided Tumor Ablation?

• DOI: 10.1016/j.jvir.2021.11.008
• 发表时间: 2022-03
• 期刊: JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
• 影响因子: 2.9
• 作者: Kamarinos, Nikiforos Vasiniotis;Vakiani, Efsevia;Fujisawa, Sho;Gonen, Mithat;Fan, Ning;Romin, Yevgeniy;Do, Richard K. G.;Ziv, Etay;Erinjeri, Joseph P.;Petre, Elena N.;Sotirchos, Vlasios S.;Camacho, Juan C.;Solomon, Stephen B.;Manova-Todorova, Katia;Sofocleous, Constantinos T.
• 通讯作者: Sofocleous, Constantinos T.

Percutaneous Microwave versus Radiofrequency Ablation of Colorectal Liver Metastases: Ablation with Clear Margins (A0) Provides the Best Local Tumor Control.

• DOI: 10.1016/j.jvir.2017.08.021
• 发表时间: 2018-03
• 期刊: Journal of vascular and interventional radiology : JVIR
• 作者: Shady W;Petre EN;Do KG;Gonen M;Yarmohammadi H;Brown KT;Kemeny NE;D'Angelica M;Kingham PT;Solomon SB;Sofocleous CT
• 通讯作者: Sofocleous CT

Kras mutation is a marker of worse oncologic outcomes after percutaneous radiofrequency ablation of colorectal liver metastases.

• DOI: 10.18632/oncotarget.19806
• 发表时间: 2017-09-12
• 期刊: Oncotarget
• 作者: Shady W;Petre EN;Vakiani E;Ziv E;Gonen M;Brown KT;Kemeny NE;Solomon SB;Solit DB;Sofocleous CT
• 通讯作者: Sofocleous CT