FISH assay identifying oral cancer patients at low risk of lymph node metastasis

FISH 检测可识别淋巴结转移风险较低的口腔癌患者

• 批准号: 8257685
• 负责人: Donna G Albertson
• 金额: $ 21.5万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-12 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8257685
• 关键词: Biological Assay; Biological Markers; Biopsy; Cancer Patient; Cause of Death; Cervical; Cervical lymph node group; Cessation of life; Chromosomes; Chromosomes, Human, Pair 20; Clinical; Collection; DNA copy number; Detection; Diagnostic; Dissection; Distant Metastasis; Evaluation; Excision; Fluorescent in Situ Hybridization; Incidence; Investigation; Label; Laboratories; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of ovary; Measurement; Medical; Methods; Molecular Profiling; Morbidity - disease rate; Neck; Neck Dissection; Neoplasm Metastasis; Office Visits; Operative Surgical Procedures; Oral; Pathologic; Patients; Primary Neoplasm; Recurrence; Risk; Risk Assessment; Sampling; Specimen; Techniques; Technology; Testing; Time; Work; base; cohort; cost; lymph nodes; malignant mouth neoplasm; melanoma; molecular marker; mouth squamous cell carcinoma; neoplastic cell; outcome forecast; prospective; research clinical testing; response; sample collection; sample fixation; treatment planning; tumor

DESCRIPTION (provided by applicant): In the USA, more people die from oral squamous cell carcinoma (SCC) than melanoma, cervical or ovarian cancer and the incidence, particularly in young people, is increasing. Neck metastasis is the primary cause of death; however, not all oral SCCs metastasize. Due to the current poor accuracy in detecting metastasis by clinical or radiographic examination prior to surgical removal of the primary cancer, neck dissection, surgery to remove the cervical (neck) lymph nodes is performed if the metastatic risk is >20% based on current risk assessment capability. Therefore, almost all oral SCC patients undergo a neck dissection which increases patient morbidity. Recent studies in our laboratories have discriminated two oral SCC subtypes with distinct molecular signatures and metastatic rates. One subtype, the 3q8pq20 subtype, is characterized by the presence of one or more of the recurrent copy number aberrations, +3q, - 8p, +8q and/or +20. The other subtype (non-3q8pq20) lacks these copy number alterations. The non-3q8pq20 subtype is associated with a low risk of metastasis (7%) compared to the 46% rate of metastasis in the 3q8pq20 subtype. This observation has been replicated in an independent oral SCC cohort. Thus, DNA copy number alterations at one or more of these loci is a biomarker identifying a group of patients at low risk for metastasis, who could be spared the potentially unnecessary major surgery required for removal of the cervical lymph nodes. In response to PA-09-158, we are proposing to develop our DNA copy number signature (+3q, -8p, +8q, +20) as a clinical test to identify the non-3q8pq20 subset of patients at low risk for metastasis. To this end, we will develop and validate a FISH-based assay to detect DNA copy number for chromosomes 3q, 8p, 8q and 20 that is suitable for analysis of lesional brush biopsies collected prior to surgery. Work will focus on sample collection (Aim 1) and copy number detection by FISH (Aim 2). We seek the combination of specimen collection technique and analysis technology that would be best suited for clinical implementation. The validated and optimized assay will be used to assess 3q8pq20 status in a subsequent multi-institutional prospective trial to establish the utility of this biomarker to identify patients who do not require a neck dissection. PUBLIC HEALTH RELEVANCE: Neck metastasis is the primary determinant for prognosis of oral cancer patients. Here, an assay for a recently identified molecular signature for tumors with low risk of metastasis will be validated and developed into a clinical test. The assay format will be suitable for analysis of patient samples collected during the period of patient evaluation prior to surgery in order to allow clinicians to confidently identify those patients at low risk for neck metastasis, who, at the time of surgical removal of their tumors, could be spared the additional major surgery required to remove the neck lymph nodes.

描述（由申请人提供）：在美国，死于口腔鳞状细胞癌（SCC）的人数多于黑素瘤、宫颈癌或卵巢癌，且发病率（尤其是年轻人）正在增加。颈部转移是死亡的主要原因;然而，并非所有口腔SCC都会转移。由于目前在手术切除原发癌、颈清扫术之前通过临床或放射学检查检测转移的准确性较差，如果根据目前的风险评估能力，转移风险>20%，则进行手术切除颈（颈）淋巴结。因此，几乎所有口腔鳞状细胞癌患者都要接受颈淋巴结清扫术，这会增加患者的发病率。我们实验室最近的研究已经区分了两种具有不同分子特征和转移率的口腔鳞状细胞癌亚型。一种亚型，3q 8 pq 20亚型，其特征在于存在一种或多种复发性拷贝数畸变，+3q、-8p、+8q和/或+20。另一种亚型（非3q 8 pq 20）缺乏这些拷贝数改变。非3q 8 pq 20亚型与低转移风险（7%）相关，而3q 8 pq 20亚型的转移率为46%。这一观察结果在一个独立的口腔SCC队列中得到了重复。因此，在这些基因座中的一个或多个基因座处的DNA拷贝数改变是识别处于低转移风险的患者组的生物标志物，这些患者可以避免切除颈部淋巴结所需的可能不必要的大手术。作为对PA-09-158的回应，我们建议开发我们的DNA拷贝数特征（+3q、-8p、+8q、+20）作为临床试验，以识别低转移风险的非3q 8 pq 20患者子集。为此，我们将开发并验证一种基于FISH的检测方法，以检测染色体3q、8 p、8 q和20的DNA拷贝数，该方法适用于分析手术前收集的病灶刷检活检标本。工作将集中在样本收集（目标1）和通过FISH检测拷贝数（目标2）。我们寻求标本采集技术和分析技术的结合，这将是最适合于临床实施。在随后的多机构前瞻性试验中，将使用经验证和优化的检测方法评估3q 8 pq 20状态，以确定该生物标志物用于识别不需要颈清扫术的患者的效用。 公共卫生相关性：颈部转移是口腔癌患者预后的主要决定因素。在这里，一种针对最近发现的低转移风险肿瘤分子特征的检测方法将得到验证，并发展为临床测试。该测定格式将适用于分析手术前患者评价期间收集的患者样本，以使临床医生能够自信地识别颈部转移风险低的患者，这些患者在手术切除肿瘤时可以避免切除颈部淋巴结所需的额外大手术。