Histologic and Immunohistochemical Biomarkers for Heavily Treated Metastatic Prostate Cancer.

重度治疗的转移性前列腺癌的组织学和免疫组织化学生物标志物。

基本信息

批准号：
9081228
负责人：
Jiaoti Huang
金额：
$ 27.11万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9081228
关键词：
Accounting Address Adenocarcinoma Androgen Receptor Biological Markers Biology Biopsy Cancer Etiology Carcinoma Castration Cells Cessation of life Clinical Clinical Research Communities Complement Development Diagnostic Disease Disease Resistance Gland Gleason Grade for Prostate Cancer Goals Histologic Histology Immunohistochemistry Indolent Life Literature Local Therapy Malignant neoplasm of prostate Metastatic Adenocarcinoma Metastatic Prostate Cancer Names Neoplasm Metastasis Neuroendocrine Carcinoma Neuroendocrine Cell Newly Diagnosed Outcome Pathologist Patient-Focused Outcomes Patients Primary Neoplasm Prognostic Factor Prostate Prostate-Specific Antigen Receptor Signaling Recurrent tumor Research Research Personnel Resistance Second Primary Neoplasms Staging Variant abiraterone base castration resistant prostate cancer disease diagnosis follow-up hormone therapy immunohistochemical markers men molecular marker new therapeutic target novel novel therapeutics outcome forecast predict clinical outcome prognostic value public health relevance targeted treatment tissue resource tumor

项目摘要

DESCRIPTION (provided by applicant): The vast majority of prostate Cancer (PCa) are histologically classified as adenocarcinoma (AdenoCa), characterized by gland formation and expression of luminal markers androgen receptor (AR) and prostate specific antigen (PSA). It is recognized that some cases of PCa are indolent and require no treatment while others can be treated by local therapies. Advanced PCa is treated by hormonal therapy which eventually fails and progresses to castration resistant PCa (CRPC). Some of the recurrent tumors do not form glands or express luminal markers and are known as small cell neuroendocrine carcinoma (SCNC). Abiraterone and Enzalutamide have recently been approved for CRPC but disease resistance develops quickly. A multi-institutional team has been assembled to biopsy metastatic PCa from 300 men who have failed both conventional and second-line hormonal therapies. From the initial 150 cases, we discovered that some tumors maintain the histology of AdenoCa, while 15% of the tumors have SCNC histology. 30% of the tumors have an intermediate histology which we have named CYBAC (Cytologically Bland Aggressive Carcinoma). While SCNC and CYBAC have uniformly poor prognosis (median survival 6-9 months), patients with metastatic AdenoCa have highly variable outcomes. The novel disease biology poses challenges to clinicians and the research community. The proposal attempts to address some of the most urgent clinical issues with the following specific aims: Aim 1. Identify biomarkers that predict the prognosis of patients with metastatic AdenoCa: We will determine if Gleason grading, which is the best predictor of clinical outcome for primary PCa, can predict the outcome of men with metastatic AdenoCa. We will also determine if certain immunohistochemistry (IHC)-based biomarkers can be used to predict outcome in these patients. Aim 2. Establishing diagnostic criteria for the newly identified PCa histologic variant CYBAC: We have established histologic criteria for the newly identified CYBAC. To help pathologists diagnose this disease entity with confidence, we will establish IHC profile of CYBAC to complement the histology criteria.

描述（由申请人提供）：绝大多数前列腺癌（PCa）在组织学上被分类为腺癌（AdenoCa），其特征在于腺体形成和管腔标志物雄激素受体（AR）和前列腺特异性抗原（PSA）的表达。有些前列腺癌病例是惰性的，不需要治疗，而另一些则可以通过局部疗法治疗。晚期前列腺癌可以通过激素疗法治疗，但最终会失败并发展为去势抵抗性前列腺癌。 (CRPC)。一些复发性肿瘤不形成腺体或表达管腔标志物，被称为小细胞神经内分泌癌 (SCNC)，最近已被批准用于 CRPC，但多机构团队已迅速发展出抗病性。我们对 300 名常规和二线激素疗法均失败的男性进行了活检，从最初的 150 例病例中发现，一些肿瘤的组织学特征仍保留。 AdenoCa，虽然 15% 的肿瘤具有 SCNC 组织学，但 30% 的肿瘤具有中间组织学，我们将其命名为 CYBAC（细胞学上温和的侵袭性癌），而 SCNC 和 CYBAC 的预后均较差（中位生存期为 6-9 个月）。转移性腺癌患者的结果差异很大，这种新的疾病生物学给大众和研究界带来了挑战，该提案试图解决一些最紧迫的问题。具有以下具体目标的临床问题：目标 1. 确定预测转移性腺癌患者预后的生物标志物：我们将确定格里森分级（原发性 PCa 临床结果的最佳预测因子）是否可以预测男性转移性腺癌的结果AdenoCa。我们还将确定某些基于免疫组织化学 (IHC) 的生物标志物是否可用于预测这些患者的结果。目标 2. 为新发现的 PCa 组织学变异建立诊断标准。 CYBAC：我们已经为新发现的 CYBAC 建立了组织学标准，为了帮助病理学家自信地诊断这种疾病，我们将建立 CYBAC 的 IHC 谱来补充组织学标准。