Raj G V, Moreno J G, Gomella L G
Division of Urology, Duke University Medical Center, Durham, North Carolina, USA.
Cancer. 1998 Apr 15;82(8):1419-42. doi: 10.1002/(sici)1097-0142(19980415)82:8<1419::aid-cncr1>3.0.co;2-4.
Most cancer detection tests currently performed are based on either antibody assays to a marker protein with altered expression in cancer patients or on imaging studies to identify characteristic lesions. Generally, for a positive result, these detection assays require that a tumor have a significant volume of cancer cells. Advances in diagnostic techniques and technology may allow for cancer detection at earlier stages, when the tumor burden is smaller and potentially more curable. The molecular techniques of polymerase chain reaction (PCR) and reverse transcriptase PCR (RT-PCR) are highly sensitive methods for detecting a small number of cancer cells. Over the past few years, numerous clinical studies have used PCR techniques to detect physical alterations of genes, such as mutations, deletions, translocations and amplification, the presence of oncogenic viruses, and the expression of genes specific to tissue, cancer, and metastasis. The current status of PCR as a method for detecting marker genes in the management of solid tumors is reviewed.
A review of the literature on the clinical utility of PCR and RT-PCR in the detection of solid tumor micrometastasis was conducted.
Amplification by PCR is a highly sensitive method to determine gene expression. A single cell expressing a tumor marker among 10-100 million lymphocytes can be detected by the PCR assay. This approach has been used to detect tumor cells in approximately 18 different solid tumor types, with melanoma and carcinoma of the breast and prostate the most widely investigated to date. PCR-based assays have been used to detect cancer cells in biopsies of solid tissue, lymph nodes, bone marrow, peripheral blood, and other body fluids. Several studies have reported a high specificity and sensitivity of tumor marker detection and a high correlation between PCR results and the presence of metastatic disease. However, in a few studies, PCR assays have not consistently demonstrated a higher sensitivity and specificity of detection than traditional modalities for many types of cancer. There has been a wide range in sensitivity and specificity among the studies, which may be partly attributed to the lack of uniformity among the PCR protocols used in different studies.
PCR can detect tumor marker-expressing cells that are otherwise undetectable by other means in patients with localized or metastatic cancer. Reports from various study groups have lacked uniformity in their protocols, and this has prevented adequate comparison. The clinical utility of this assay as a tool for the prognosis and management of cancer patients remains and area of active investigation. PCR is a powerful tool in the study of the biology of cancer metastasis and will likely serve as a useful adjunct to clinical decision-making in the future.
目前进行的大多数癌症检测试验要么基于针对癌症患者中表达改变的标志物蛋白的抗体检测，要么基于成像研究以识别特征性病变。一般来说，对于阳性结果，这些检测试验要求肿瘤具有大量癌细胞。诊断技术和科技的进步可能使癌症在更早阶段被检测出来，此时肿瘤负荷较小且可能更易治愈。聚合酶链反应（PCR）和逆转录聚合酶链反应（RT-PCR）的分子技术是检测少量癌细胞的高灵敏度方法。在过去几年中，众多临床研究已使用PCR技术来检测基因的物理改变，如突变、缺失、易位和扩增，致癌病毒的存在，以及组织、癌症和转移所特有的基因表达。本文综述了PCR作为检测实体瘤标志物基因方法的现状。
对关于PCR和RT-PCR在检测实体瘤微转移中的临床应用的文献进行综述。
通过PCR进行扩增是确定基因表达的高灵敏度方法。PCR检测可在1亿至10亿个淋巴细胞中检测到单个表达肿瘤标志物的细胞。这种方法已被用于检测约18种不同实体瘤类型中的肿瘤细胞，其中黑色素瘤以及乳腺癌和前列腺癌是迄今为止研究最广泛的。基于PCR的检测已被用于检测实体组织活检、淋巴结、骨髓、外周血和其他体液中的癌细胞。几项研究报告了肿瘤标志物检测具有高特异性和灵敏度，以及PCR结果与转移性疾病存在之间具有高度相关性。然而，在一些研究中，对于许多类型的癌症，PCR检测并未始终显示出比传统方法更高的检测灵敏度和特异性。不同研究之间的灵敏度和特异性差异很大，这可能部分归因于不同研究中使用的PCR方案缺乏一致性。
PCR可检测局限性或转移性癌症患者中其他方法无法检测到的表达肿瘤标志物的细胞。各个研究组的报告在方案上缺乏一致性，这妨碍了充分的比较。该检测作为癌症患者预后和管理工具的临床效用仍是一个积极研究的领域。PCR是癌症转移生物学研究中的有力工具，未来可能会成为临床决策的有用辅助手段。
