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肿瘤标记物
感谢王为老师提供本文，将原文翻译成中文，以供学习。
什么是肿瘤标记物?
肿瘤标记物由肿瘤（癌）细胞产生或机体其他细胞对肿瘤或其他良性（非肿瘤性）疾病产生的反应。大部分肿瘤标记物由正常细胞或癌细胞在非常高水平的癌性环境下制成；在血液、尿液、粪便、肿瘤组织或其他组织或一些患癌病人的体液中都可见肿瘤标记物。大部分肿瘤标记物是蛋白质类。最近，基因表达模式和DNA变化也开始用于肿瘤标记物。
许多不同的肿瘤标记物具有其特性，应用于临床。一部分与1种类型肿瘤相关，其他标记物与2种或更多肿瘤类型相关。尚未发现一种“全能”肿瘤标记物能用于检测任何类型肿瘤。
一些肿瘤标记物的应用范围有限，有时非肿瘤疾病可引起肿瘤标记物水平增高；不是每一种肿瘤都有特异性高水平表达的肿瘤标记物，每一种类型的肿瘤也未必都有明确的肿瘤标记物。
如何使用肿瘤标记物?
肿瘤标记物的应用有助于肿瘤的检测、诊断和管理。虽然肿瘤标记物水平升高提示肿瘤存在，但如果只是单一结果并不能足以诊断肿瘤，因此，对活检组织诊断肿瘤时，常联合应用肿瘤标记物。
治疗前检测肿瘤标记物水平有助于医生制定合适的治疗方案。部分类型的肿瘤其肿瘤标记物水平反映了疾病的分期（程度）和/或患者的预后（疾病可能发展结果或进程），为肿瘤分期提供更多的信息。
癌症治疗期间，可定期检测肿瘤标记物，肿瘤标记物水平降低或回归正常水平提示肿瘤对治疗有反应，如无改变或升高则提示对治疗无反应。
肿瘤标记物也可用于治疗结束后复发评价（肿瘤复发）。
如何判读肿瘤标记物?
医生对肿瘤组织取样或抽取体液送至实验室，实验室工作人员应用各种方法检测肿瘤标记物表达水平。
如果肿瘤标记物用于检测是否需要治疗或是否有复发，需要对多样本进行标记物表达水平的检测，通常一系列的检测结果（显示标记物水平是否升高、无改变或降低）比单一的检测结果更有意义。
NCI是否有肿瘤标记物应用指南?
NCI尚无这种应用指南。但一些国家和国际机构有部分肿瘤中肿瘤标记物的应用指南：
ASCO发布了包括乳腺癌、结肠癌、肺癌和其他肿瘤的肿瘤标记物的临床实践指南。
国家临床生化科学院临床发布了实验室医学实践指南，包括肿瘤标记物在临床实践中的应用：质量要求退出免责声明。
哪些常用肿瘤标记物及其应用范围?
多项肿瘤标记物现在常可广泛用于多种类型肿瘤，大部分肿瘤标记物适用于实验室（标准见临床实验室修正案），一些肿瘤标记物仅适用于实验。常用肿瘤标记物见下文。
ALK 基因重排和过表达
肿瘤类型：非小细胞肺癌和间变性大细胞淋巴瘤
组织分析：肿瘤
应用：有助于明确治疗和预后
甲胎蛋白（AFP）
肿瘤类型：肝癌和生殖细胞肿瘤
组织分析：血液
应用：有助于肝癌的诊断、判断治疗后反应；评估生殖细胞肿瘤的分期、预后和治疗后反应
β-2-微球蛋白
肿瘤类型：多发性骨髓瘤、慢性淋巴细胞白血病和部分淋巴瘤
组织分析：血液、尿液或脑脊髓液
应用：判断预后和治疗后反应
β-人绒毛膜促性腺激素（β-hCG）
肿瘤类型：绒毛膜癌和生殖细胞肿瘤
组织分析：尿液和血液
应用：评估分期、预后和治疗后反应
BRCA1和BRCA2基因突变
肿瘤类型：卵巢癌
组织分析：血液
应用：判断是否适用于特殊类型靶向治疗
BCR-ABL融合基因（费城染色体）
肿瘤类型：慢性髓性白血病、急性淋巴母细胞性白血病和急性髓性白血病
组织分析：血液和/骨髓
应用：明确诊断、预测靶向治疗反应和监测疾病状态
BRAF V600突变
肿瘤类型：皮肤黑色素瘤和结直肠癌
组织分析：肿瘤
应用：选择靶向治疗疗效最好的患者
CD117
肿瘤类型：胃肠道间质瘤和粘膜黑色素瘤
组织分析：肿瘤
应用：有助于诊断和确定治疗
CA15-3/CA27.29
肿瘤类型：乳腺癌
组织分析：血液
应用：评估治疗是否有效或疾病有无复发
CA19-9
肿瘤类型：胰腺癌、胆囊癌、胆管癌和胃癌
组织分析：血液
应用：评估治疗是否有效
肿瘤类型：卵巢癌
组织分析：血液
应用：有助于诊断、评估治疗后反应和肿瘤复发
Calcitonin 降钙素
肿瘤类型：甲状腺髓样癌
组织分析：血液
应用：明确诊断、判断治疗是否有效和评估复发
癌胚抗原（CEA）
肿瘤类型：结直肠癌和部分癌
组织分析：血液
应用：跟踪癌症治疗疗效或是否复发
肿瘤类型：非霍奇金淋巴瘤
组织分析：血液
应用：明确是否适用于靶向治疗
嗜铬粒蛋白 A (CgA)
肿瘤类型：神经内分泌肿瘤
组织分析：血液
应用：有助于诊断、评估治疗反应和复发
染色体3、 7、 17和 9p21
肿瘤类型：膀胱癌
组织分析：尿液
应用：有助于监测肿瘤是否复发
上皮源性循环肿瘤细胞(CELLSEARCH®)
肿瘤类型：转移性乳腺癌、前列腺癌和结直肠癌
组织分析：血液
应用：以确定临床决策和评估预后
21-1 细胞角蛋白片段21-1
肿瘤类型：肺癌
组织分析：血液
应用：有助于复发监测
EGFR基因突变分析
肿瘤类型：非小细胞肺癌
组织分析：肿瘤
应用：有助于确定治疗方案和预后
雌激素受体（ER）/孕激素受体（PR）
肿瘤类型：乳腺癌
组织分析：肿瘤
应用：明确是否采用激素治疗和靶向药物的应用
纤维蛋白/纤维蛋白原
肿瘤类型：膀胱癌
组织分析：尿液
应用：监测预后和治疗反应
肿瘤类型：卵巢癌
组织分析：血液
应用：制定癌症治疗方案，评估疾病预后和复发监测
HER2/neu基因扩增或蛋白过表达
肿瘤类型：乳腺癌、胃癌和食管胃连接处腺癌
组织分析：肿瘤
应用：明确是否适用靶向治疗
免疫球蛋白
肿瘤类型：多发性骨髓瘤和华氏巨球蛋白血症
组织分析：血液和尿液
应用：明确诊断，评估治疗反应和复发
KRAS基因突变分析
肿瘤类型：结直肠癌和非小细胞肺癌
组织分析：肿瘤
应用：明确是否适用特殊类型的靶向治疗
乳酸脱氢酶
肿瘤类型：生殖细胞肿瘤、淋巴瘤、白血病、黑色素瘤和神经母细胞瘤
组织分析：血液
应用：评估分期、预后和治疗反应
神经元特异性烯醇酶(NSE)
肿瘤类型：小细胞肺癌和神经母细胞瘤
组织分析：血液
应用：有助于明确诊断和评估治疗反应
核基质蛋白22
肿瘤类型：膀胱癌
组织分析：尿液
应用：监测治疗反应
程序死亡配体1 (PD-L1)
肿瘤类型：非小细胞肺癌
组织分析：肿瘤
应用：明确是否适用特殊类型的靶向治疗
前列腺特异性抗原(PSA)
肿瘤类型：前列腺癌
组织分析：血液
应用：有助于明确诊断、评估治疗反应和复发
甲状腺球蛋白
肿瘤类型：甲状腺癌
组织分析：血液
应用：评估治疗反应和复发
尿激酶纤维蛋白溶酶原激活剂(uPA)和纤维蛋白沉吟酶原激活因子抑制物(PAI-1)
肿瘤类型：乳腺癌
组织分析：肿瘤
应用：明确癌侵袭性和指导治疗
5-蛋白标签(OVA1®)
肿瘤类型：卵巢癌
组织分析：血液
应用：针对可疑卵巢癌进行盆腔肿物术前评估
21-基因标签(Oncotype DX®)
肿瘤类型：乳腺癌
组织分析：肿瘤
应用：评估复发风险
70-基因标签(Mammaprint®)
肿瘤类型：乳腺癌
组织分析：肿瘤
应用：评估复发风险
肿瘤标记物能否用于癌症筛查？
肿瘤标记物可用于评估肿瘤治疗反应和预后，研究者希望其能应用于肿瘤筛查，以期在出现症状前尽早检测出癌症。作为筛查检测，需要有非常高的敏感性（能正确检测出患病人群）和特异性（能正确检测出非患病人群）。如果检测具有高度敏感性，能检测出大部分患病人群——假阴性结果非常少；如果检测具有高度特异性，在无病人群中仅少许人群患病，换句话说是假阳性结果少。
虽然肿瘤标记广泛用于明确肿瘤是否治疗有效，或评估是否复发，尚无明确数据证明肿瘤标记物具有足够的敏感性和特异性，以用于癌症筛查。
例如：PSA检测血液中PSA水平，常用于前列腺癌的筛查，但良性前列腺病变和前列腺癌都可导致PSA水平升高，大部分PSA增高者未患前列腺癌。最初两个大样本随机对照实验，NCI发起的前列腺癌、肺癌、结直肠癌和卵巢癌筛查实验（PLCO）和欧洲对前列腺癌的随机研究显示PSA检测仅能轻微减少前列腺癌患者的死亡人数。尚不明确对前列腺癌患者后续检测PSA筛查是否是利大于弊，有许多患者在发病前无任何表现。
同样结果示，有时卵巢癌患者血液检测可见CA125升高，但在良性病变中CA125也会升高，尚无足够的敏感性和特异性证明CA125检测联合阴道超声可用于女性卵巢癌平均发病风险的筛查。在对后期发生卵巢癌的女性血液进行28种卵巢癌潜在标记物分析发现没有一种标记物能像CA125一样用于女性卵巢癌平均发病风险的检测。
现在有哪些研究开发更准确的肿瘤标记物？
癌症研究人员现在转向蛋白组学研究（研究蛋白质结构、功能和表型），希望发现新的标记物能发现早期疾病，预测治疗效果，或预测治疗结束后癌症复发机率。
科学家评估基因表达模式对患者预后和治疗反应检测效果。如，在NCI发起的个体化治疗结果（Rx）或TAILORx提示近期诊断了激素受体阳性、HER-2阴性、淋巴结阴性，行外科手术治疗的乳腺癌女性， 行单独激素治疗，21基因复发评分非常低提示复发机率非常低，无须额外化疗。目前进行的实验是 检测21基因中等程度复发风险的女性是否激素治疗加化疗效果优于单独激素治疗。
NCI在对癌症诊断新工具和方法的更多研究相关资料见诊断研究页面。
附全文：
Tumor markers
What are tumor markers?
Tumor markers are substances that are produced by cancer or by other cells of the body in response to cancer or certain benign (noncancerous) conditions. Most tumor markers are made by normal cells as well as by cancer cells; however, they are produced at much higher levels in cancerous conditions. These substances can be found in the blood, urine, stool, tumor tissue, or other tissues or bodily fluids of some patients with cancer. Most tumor markers are proteins. However, more recently, patterns of gene expression and changes to DNA have also begun to be used as tumor markers.
Many different tumor markers have been characterized and are in clinical use. Some are associated with only one type of cancer, whereas others are associated with two or more cancer types. No “universal” tumor marker that can detect any type of cancer has been found.
There are some limitations to the use of tumor markers. Sometimes, noncancerous conditions can cause the levels of certain tumor markers to increase. In addition, not everyone with a particular type of cancer will have a higher level of a tumor marker associated with that cancer. Moreover, tumor markers have not been identified for every type of cancer.
How are tumor markers used in cancer care?
Tumor markers are used to help detect, diagnose, and manage some types of cancer. Although an elevated level of a tumor marker may suggest the presence of cancer, this alone is not enough to diagnose cancer. Therefore, measurements of tumor markers are usually combined with other tests, such as biopsies, to diagnose cancer.
Tumor marker levels may be measured before treatment to help doctors plan the appropriate therapy. In some types of cancer, the level of a tumor marker reflects the stage (extent) of the disease and/or the patient’s prognosis (likely outcome or course of disease). More information about cancer staging is available on the Staging page.
Tumor markers may also be measured periodically during cancer therapy. A decrease in the level of a tumor marker or a return to the marker’s normal level may indicate that the cancer is responding to treatment, whereas no change or an increase may indicate that the cancer is not responding.
Tumor markers may also be measured after treatment has ended to check for recurrence (the return of cancer).
How are tumor markers measured?
A doctor takes a sample of tumor tissue or bodily fluid and sends it to a laboratory, where various methods are used to measure the level of the tumor marker.
If the tumor marker is being used to determine whether treatment is working or whether there is a recurrence, the marker’s level will be measured in multiple samples taken over time. Usually these “serial measurements,” which show whether the level of a marker is increasing, staying the same, or decreasing, are more meaningful than a single measurement.
Does NCI have guidelines for the use of tumor markers?
NCI does not have such guidelines. However, some national and international organizations do have guidelines for the use of tumor markers for some types of cancer:
· The American Society of Clinical Oncology (ASCO) has published clinical practice guidelinesExit Disclaimer on a variety of topics, including tumor markers for breast cancer, colorectal cancer, lung cancer, and others.
· The National Academy of Clinical Biochemistry publishes laboratory medicine practice guidelines, including Use of Tumor Markers in Clinical Practice: Quality RequirementsExit Disclaimer, which focuses on the appropriate use of tumor markers for specific cancers.
What tumor markers are currently being used, and for which cancer types?
A number of tumor markers are currently being used for a wide range of cancer types. Although most of these can be tested in laboratories that meet standards set by the Clinical Laboratory Improvement Amendments, some cannot be and may therefore be considered experimental. Tumor markers that are currently in common use are listed below.
ALK gene rearrangements and overexpression
· Cancer types: Non-small cell lung cancer and anaplastic large cell lymphoma
· Tissue analyzed: Tumor
· How used: To help determine treatment and prognosis
Alpha-fetoprotein (AFP)
· Cancer types: Liver cancer and germ cell tumors
· Tissue analyzed: Blood
· How used: To help diagnose liver cancer and follow response to treatment; to assess stage, prognosis, and response to treatment of germ cell tumors
Beta-2-microglobulin (B2M)
· Cancer types: Multiple myeloma, chronic lymphocytic leukemia, and some lymphomas
· Tissue analyzed: Blood, urine, or cerebrospinal fluid
· How used: To determine prognosis and follow response to treatment
Beta-human chorionic gonadotropin (Beta-hCG)
· Cancer types: Choriocarcinoma and germ cell tumors
· Tissue analyzed: Urine or blood
· How used: To assess stage, prognosis, and response to treatment
BRCA1 and BRCA2 gene mutations
· Cancer type: Ovarian cancer
· Tissue analyzed: Blood
· How used: To determine whether treatment with a particular type of targeted therapy is appropriate
BCR-ABL fusion gene (Philadelphia chromosome)
· Cancer type: Chronic myeloid leukemia, acute lymphoblastic leukemia, and acute myelogenous leukemia
· Tissue analyzed: Blood and/or bone marrow
· How used: To confirm diagnosis, predict response to targeted therapy, and monitor disease status
BRAF V600 mutations
· Cancer types: Cutaneous melanoma and colorectal cancer
· Tissue analyzed: Tumor
· How used: To select patients who are most likely to benefit from treatment with certain targeted therapies
· Cancer types: Gastrointestinal stromal tumor and mucosal melanoma
· Tissue analyzed: Tumor
· How used: To help in diagnosing and determining treatment
CA15-3/CA27.29
· Cancer type: Breast cancer
· Tissue analyzed: Blood
· How used: To assess whether treatment is working or disease has recurred
CA19-9
· Cancer types: Pancreatic cancer, gallbladder cancer, bile duct cancer, and gastric cancer
· Tissue analyzed: Blood
· How used: To assess whether treatment is working
· Cancer type: Ovarian cancer
· Tissue analyzed: Blood
· How used: To help in diagnosis, assessment of response to treatment, and evaluation of recurrence
· Cancer type: Medullary thyroid cancer
· Tissue analyzed: Blood
· How used: To aid in diagnosis, check whether treatment is working, and assess recurrence
Carcinoembryonic antigen (CEA)
· Cancer types: Colorectal cancer and some other cancers
· Tissue analyzed: Blood
· How used: To keep track of how well cancer treatments are working or check if cancer has come back
· Cancer type: Non-Hodgkin lymphoma
· Tissue analyzed: Blood
· How used: To determine whether treatment with a targeted therapy is appropriate
Chromogranin A (CgA)
· Cancer type: Neuroendocrine tumors
· Tissue analyzed: Blood
· How used: To help in diagnosis, assessment of treatment response, and evaluation of recurrence
Chromosomes 3, 7, 17, and 9p21
· Cancer type: Bladder cancer
· Tissue analyzed: Urine
· How used: To help in monitoring for tumor recurrence
Circulating tumor cells of epithelial origin (CELLSEARCH®)
· Cancer types: Metastatic breast, prostate, and colorectal cancers
· Tissue analyzed: Blood
· How used: To inform clinical decision making, and to assess prognosis
Cytokeratin fragment 21-1
· Cancer type: Lung cancer
· Tissue analyzed: Blood
· How used: To help in monitoring for recurrence
EGFR gene mutation analysis
· Cancer type: Non-small cell lung cancer
· Tissue analyzed: Tumor
· How used: To help determine treatment and prognosis
Estrogen receptor (ER)/progesterone receptor (PR)
· Cancer type: Breast cancer
· Tissue analyzed: Tumor
· How used: To determine whether treatment with hormone therapy and some targeted therapies is appropriate
Fibrin/fibrinogen
· Cancer type: Bladder cancer
· Tissue analyzed: Urine
· How used: To monitor progression and response to treatment
· Cancer type: Ovarian cancer
· Tissue analyzed: Blood
· How used: To plan cancer treatment, assess disease progression, and monitor for recurrence
HER2/neu gene amplification or protein overexpression
· Cancer types: Breast cancer, gastric cancer, and gastroesophageal junction adenocarcinoma
· Tissue analyzed: Tumor
· How used: To determine whether treatment with certain targeted therapies is appropriate
Immunoglobulins
· Cancer types: Multiple myeloma and Waldenström macroglobulinemia
· Tissue analyzed: Blood and urine
· How used: To help diagnose disease, assess response to treatment, and look for recurrence
KRAS gene mutation analysis
· Cancer types: Colorectal cancer and non-small cell lung cancer
· Tissue analyzed: Tumor
· How used: To determine whether treatment with a particular type of targeted therapy is appropriate
· Cancer types: Germ cell tumors, lymphoma, leukemia, melanoma, and neuroblastoma
· Tissue analyzed: Blood
· How used: To assess stage, prognosis, and response to treatment
Neuron-specific enolase (NSE)
· Cancer types: Small cell lung cancer and neuroblastoma
· Tissue analyzed: Blood
· How used: To help in diagnosis and to assess response to treatment
Nuclear matrix protein 22
· Cancer type: Bladder cancer
· Tissue analyzed: Urine
· How used: To monitor response to treatment
Programmed death ligand 1 (PD-L1)
· Cancer type: Non-small cell lung cancer
· Tissue analyzed: Tumor
· How used: To determine whether treatment with a particular type of targeted therapy is appropriate
Prostate-specific antigen (PSA)
· Cancer type: Prostate cancer
· Tissue analyzed: Blood
· How used: To help in diagnosis, assess response to treatment, and look for recurrence
· Cancer type: Thyroid cancer
· Tissue analyzed: Blood
· How used: To evaluate response to treatment and look for recurrence
Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1)
· Cancer type: Breast cancer
· Tissue analyzed: Tumor
· How used: To determine aggressiveness of cancer and guide treatment
5-Protein signature (OVA1®)
· Cancer type: Ovarian cancer
· Tissue analyzed: Blood
· How used: To pre-operatively assess pelvic mass for suspected ovarian cancer
21-Gene signature (Oncotype DX®)
· Cancer type: Breast cancer
· Tissue analyzed: Tumor
· How used: To evaluate risk of recurrence
70-Gene signature (Mammaprint®)
· Cancer type: Breast cancer
· Tissue analyzed: Tumor
· How used: To evaluate risk of recurrence
Can tumor markers be used in cancer screening?
Because tumor markers can be used to assess the response of a tumor to treatment and for prognosis, researchers have hoped that they might also be useful in screening tests that aim to detect cancer early, before there are any symptoms. For a screening test to be useful, it should have very high sensitivity (ability to correctly identify people who have the disease) and specificity (ability to correctly identify people who do not have the disease). If a test is highly sensitive, it will identify most people with the disease—that is, it will result in very few false-negative results. If a test is highly specific, only a small number of people will test positive for the disease who do not have it—in other words, it will result in very few false-positive results.
Although tumor markers are extremely useful in determining whether a tumor is responding to treatment or assessing whether it has recurred, no tumor marker identified to date is sufficiently sensitive or specific to be used on its own to screen for cancer.
For example, the prostate-specific antigen (PSA) test, which measures the level of PSA in the blood, is often used to screen men for prostate cancer. However, an increased PSA level can be caused by benign prostate conditions as well as by prostate cancer, and most men with an elevated PSA level do not have prostate cancer. Initial results from two large randomized controlled trials, the NCI-sponsored Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the European Randomized Study of Screening for Prostate Cancer, showed that PSA testing at best leads to only a small reduction in the number of prostate cancer deaths. Moreover, it is not clear whether the benefits of PSA screening outweigh the harms of follow-up diagnostic tests and treatments for cancers that in many cases would never have threatened a man’s life.
Similarly, results from the PLCO trial showed that CA-125, a tumor marker that is sometimes elevated in the blood of women with ovarian cancer but can also be elevated in women with benign conditions, is not sufficiently sensitive or specific to be used together with transvaginal ultrasound to screen for ovarian cancer in women at average risk of the disease. An analysis of 28 potential markers for ovarian cancer in blood from women who later went on to develop ovarian cancer found that none of these markers performed even as well as CA-125 at detecting the disease in women at average risk.
What kind of research is under way to develop more accurate tumor markers?
Cancer researchers are turning to proteomics (the study of protein structure, function, and patterns of expression) in hopes of developing new biomarkers that can be used to identify disease in its early stages, to predict the effectiveness of treatment, or to predict the chance of cancer recurrence after treatment has ended.
Scientists are also evaluating patterns of gene expression for their ability to help determine a patient’s prognosis or response to therapy. For example, results of the NCI-sponsored Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx , showed that for women recently diagnosed with lymph node–negative, hormone receptor–positive, HER2-negative breast cancer who had undergone surgery, those with the lowest 21-gene (Oncotype Dx®) recurrence scores had very low recurrence rates when given hormone therapy alone and thus can be spared chemotherapy. The trial is ongoing to see whether women at intermediate risk of recurrence, based on the 21-gene test, do better with chemotherapy in addition to hormone therapy than with hormone therapy alone.
More information on NCI’s role in supporting research on novel tools and methods for diagnosing cancer is available on the Diagnosis research page.
Selected References
1. Bigbee W, Herberman RB. Tumor markers and immunodiagnosis. In: Bast RC Jr., Kufe DW, Pollock RE, et al., editors. Cancer Medicine. 6th ed. Hamilton, Ontario, Canada: BC Decker Inc., 2003.
2. Andriole G, Crawford E, Grubb R, et al. Mortality results from a randomized prostate-cancer screening trial. New England Journal of Medicine 2009; 360(13):1310–1319. [PubMed Abstract]
3. Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. New England Journal of Medicine 2009; 360(13):1320–1328. [PubMed Abstract]
4. Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 2011; 305(22):2295–2303. [PubMed Abstract]
5. Cramer DW, Bast RC Jr, Berg CD, et al. Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prevention Research 2011; 4(3):365–374. [PubMed Abstract]
6. Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. New England Journal of Medicine 2015; First published online September 28, 2015. doi: 10.1056/NEJMoa1510764Exit Disclaimer.
Related Resources
· Prostate-Specific Antigen (PSA) Test
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