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。

• 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
• 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

 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（由适用提供）：绝大多数前列腺癌（PCA）在组织学上分类为腺癌（腺癌），其特征是腺体标记物的腺体形成和表达雄激素受体（AR）和前列腺特异性抗原（PSA）。人们认识到，某些PCA病例是懒惰的，不需要治疗，而其他情况则可以通过局部疗法进行治疗。高级PCA通过荷尔蒙疗法进行治疗，激素疗法均匀失败并发展为耐castration PCA（CRPC）。某些复发性肿瘤不形成腺体或表达腔标记物，被称为小细胞神经内分泌癌（SCNC）。阿比罗酮和enzalutamide最近被批准用于CRPC，但抗病性迅速发展。一支多机构的团队已从300名失败的常规和二线荷尔蒙疗法的男性进行活检转移PCA组装。从最初的150例病例开始，我们发现某些肿瘤维持了腺癌的组织学，而15％的肿瘤具有SCNC组织学。 30％的肿瘤具有中间的组织学，我们将其命名为CYBAC（细胞学上平淡的攻击性癌）。尽管SCNC和CYBAC的预后均匀（中位存活6-9个月）均匀，但转移性腺癌患者的预后差异很大。新型疾病生物学对临床医生和研究界构成了挑战。该提案试图解决以下具体目的的一些最紧急临床问题：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Gleason Geleson分级是否是GLEASON CARMATION的最佳预测，这是原发性PCA的临床结果的最佳预测指标，可以预测男性转移性Adenoca的结果。我们还将确定是否可以使用某些免疫组织化学（IHC）生物标志物来预测这些患者的结果。 AIM 2。建立新确定的PCA组织学变种Cybac的诊断标准：我们已经建立了新确定的Cybac的组织学标准。为了帮助病理学家充满信心地诊断该疾病实体，我们将建立CYBAC的IHC概况以完成组织学标准。