Histologic and Immunohistochemical Biomarkers for Heavily Treated Metastatic Prostate Cancer.

 描述(申请人提供)：绝大多数前列腺癌(PCa)在组织学上被归类为腺癌(AdenoCa)，其特征是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。人们认识到，一些前列腺癌病例是惰性的，不需要治疗，而另一些病例可以通过局部治疗来治疗。晚期前列腺癌的治疗是通过激素治疗，但最终失败并进展为抗去势的前列腺癌(CRPC)。一些复发的肿瘤不形成腺体或表达腔标志，被称为小细胞神经内分泌癌(SCNC)。阿比特龙和恩扎鲁胺最近被批准用于CRPC，但抗病能力发展迅速。一个多机构的团队已经聚集在一起，对300名同时接受常规和二线激素治疗失败的转移性前列腺癌患者进行活检。从最初的150例中，我们发现一些肿瘤保持了腺钙的组织学，而15%的肿瘤具有SCNC组织学。30%的肿瘤具有中间组织学，我们称之为CyBAC(细胞学Bland侵袭性癌)。虽然SCNC和CyBAC的预后都很差(中位生存期6-9个月)，但转移性腺癌患者的预后差异很大。新的疾病生物学给临床医生和研究界带来了挑战。该提案试图解决一些最紧迫的临床问题，具体目标如下：目的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分级是否可以预测转移性腺癌患者的结果。格里森分级是预测原发PCa临床结果的最佳指标。我们还将确定某些基于免疫组织化学(IHC)的生物标记物是否可以用于预测这些患者的预后。目的2.建立新发现的前列腺癌组织变异体CyBAC的诊断标准：我们已经为新发现的CyBAC建立了组织学标准。为了帮助病理学家有信心地诊断这一疾病实体，我们将建立CyBAC的IHC图谱，以补充组织学标准。

 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.