Department of Solid Tumor Oncology, Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Curr Treat Options Oncol. 2013 Dec;14(4):623-33. doi: 10.1007/s11864-013-0259-z.
Patients with cancer of unknown primary are common and can present in a variety of ways with different histological features. Despite best clinical effort in pretreatment diagnostic workup, many patients classified as having cancer of unknown primary (CUP) often are still left with no definitive diagnosis of the primary organ or tissue of origin to account for the metastatic disease. Whereas advances in immunohistochemical techniques have improved the diagnostic yield to some extent, the challenges remain substantial for most patients with CUP in whom initial therapy is typically chosen empirically. In recent years, development of molecular gene profiling of tumor offers new possibilities to better characterize, diagnose, and classify the tissue of origin of various metastatic CUP to better inform optimal therapy. The premise behind the development of improved diagnostic tools to better diagnose the organ or tissue of origin for metastatic disease of unknown primary is that an organ/tissue-specific tailored therapy of choice would favorably impact the treatment outcome. There are now three commercially available molecular profiling platforms for the purpose of diagnosing the tissue of origin in the otherwise CUP patients: 1) bioTheranostics: Cancer TYPE ID® (qRT-PCR for mRNA); 2) Pathworks®: Tissue of origin test (microarray for mRNA expression); and 3) Rosetta Genomics-Prometheus: miRview™ mets (ProOnc Tumor SourceDxT) (qRT-PCR for microRNA). Whereas these are new technologic platforms that offer new promise for better diagnostics and perhaps better therapeutic strategies in cancer therapy, each of the platforms has its own strengths and limitations due to their test of choice and assay source materials and technical platform itself. However, a fundamental question that needs be further addressed regarding the utility of these novel molecular profiling assays is whether they represent more superior approaches than genomic profiling assays using rapidly emerging cancer genomics next-generation sequencing (NSG) platforms. Because cancer is nowadays understood as genomic disease, the genomic alterations (e.g., mutations, copy number variations, chromosomal translocations, splicing variants) may offer more important insights into the cancer pathogenesis. More importantly, these genomic information may be more relevant in guiding personalized/precision cancer therapy than merely empiric chemotherapy based on tissue/organ-of-origin information. Ideally, further comparative studies and demonstration of utilities would be needed and eagerly anticipated to determine which diagnostic approach ultimately could impact the clinical outcome of patients with CUP.
患有不明原发灶癌症的患者较为常见，其临床表现和组织学特征多种多样。尽管在预处理诊断工作中付出了最大的临床努力，但许多被归类为不明原发灶癌症（CUP）的患者仍然无法明确诊断出转移疾病的原发器官或组织。尽管免疫组织化学技术的进步在一定程度上提高了诊断率，但对于大多数 CUP 患者来说，挑战仍然很大，因为他们的初始治疗通常是经验性选择的。近年来，肿瘤分子基因谱的发展为更好地描述、诊断和分类各种转移性 CUP 的组织来源提供了新的可能性，从而更好地为最佳治疗提供信息。开发更好的诊断工具以更好地诊断不明原发灶转移疾病的器官或组织的前提是，选择针对特定器官/组织的定制治疗方案将有利地影响治疗结果。目前有三种商业上可用于诊断 otherwise CUP 患者组织来源的分子谱分析平台：1）生物治疗诊断学：Cancer TYPE ID®（mRNA 的 qRT-PCR）；2）Pathworks®：组织来源测试（mRNA 表达的微阵列）；3）Rosetta Genomics-Prometheus：miRview™ mets（ProOnc Tumor SourceDxT）（microRNA 的 qRT-PCR）。尽管这些是提供更好的诊断和癌症治疗中更好的治疗策略的新的技术平台，但由于它们的测试选择、检测来源材料和技术平台本身，每个平台都有其自身的优势和局限性。然而，这些新型分子谱分析检测的实用性需要进一步解决的一个基本问题是，它们是否代表比利用快速发展的癌症基因组下一代测序（NGS）平台进行基因组谱分析更优越的方法。因为现在人们认为癌症是一种基因组疾病，所以基因组改变（例如突变、拷贝数变异、染色体易位、剪接变体）可能为癌症发病机制提供更重要的见解。更重要的是，这些基因组信息可能比基于组织/器官来源信息的经验性化疗更有助于指导个性化/精准癌症治疗。理想情况下，需要并迫切期待进一步的比较研究和效用证明，以确定哪种诊断方法最终可以影响 CUP 患者的临床结果。
