肿瘤标志物的临床应用原则.ppt
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参见附件(3300KB)。
肿瘤生物标志物的
临床应用原则
什么是"癌症"
The term 'cancer' refers to a disparate group of malignant diseases that have one thing in common: uncontrolled division of the cells of an organ or tissue. A mass of cancer cells is known as a tumour. The uncontrolled growth of a tumour results in destruction of surrounding healthy tissue. Spread of tumour cells via the blood or lymphatic system can lead to the formation of secondary growths, or metastases, in other organs or tissues.
肿瘤严重威胁人类健康和生命
? 全球因癌症每年死亡人数约600万
? 我国因癌症死亡数每年约130万
? 按目前趋势预测在2020年随全球人口达80亿，将有2000万新发癌症病人，每年死亡人数达1200万。
? 所以肿瘤的早期发现和早期诊断对肿瘤的预防和治疗至关重要。
NCI年度报告
? Americans' risk of getting and dying from cancer continues to decline and survival rates for many cancers continue to improve. The "Annual Report to the Nation on the Status of Cancer, 1975-2001".
? cancer incidence rates dropped 0.5 percent per year from 1991 to 2001,?Death rates from all cancers combined dropped 1.1 percent per year from 1993 to 2001.
? According to the report's authors, the new data reflect progress in prevention, early detection, and treatment.
定义
中华医学会检验医学分会肿瘤标志物专家委员会，中华检验医学杂志 2004；27(6)：393
? 肿瘤标志物(TM)是指在恶性肿瘤发生和增殖过程中，由肿瘤细胞的基因表达而合成分泌的或是由机体对肿瘤反应而异常产生和/或升高的，反映肿瘤存在和生长的一类物质，包括蛋白质、激素、酶(同工酶)、多胺及癌基因产物等。TM存在于病人的血液、体液、细胞或组织中，可用生物化学、免疫学及分子生物学等方法测定，且对肿瘤的辅助诊断、鉴别诊断、观察疗效、监测复法以及预后评价具有一定的价值。
ACS 定义
? Tumor markers are substances produced by cancer cells and sometimes normal cells. They can be found in large amounts in the blood or urine of some patients with cancer. Less often, they can also be found in large amounts in the blood or urine of people who do not have cancer.
理想的肿瘤指标
? 高特异性
? 高灵敏度
? 组织特异性
? 与肿瘤分型和病程有关
? 与预后相关
? 可靠的检测值
癌症的发生与发展过程
? 起动(initiation)
? 促动(promotion)
? 转化(conversion)
? 进展(progression)
肿瘤标志物分类
> 胚胎性，如AFP、CEA等
> 糖类抗原，如CA19-9、CA72-4
> 酶类，如ACP、同工酶等
> 激素类，如hCG、甲状旁腺素等
> 蛋白类，如Bence Jones 蛋白
> 基因类，包括促癌基因、抑癌基因等
检测方法
六十年代RIA
七十年代ELISA
八十年代FIA/CL/CL Enh.
九十年代 ECL
目前Bio-Chips
第一个肿瘤标志物可追溯到1846年由H Bence-Jones所证实的本周氏蛋白(Bence Jones Protein)，150余年后的今天，人们已先后发现了数十种对恶性肿瘤具有一定辅助诊断价值的肿瘤标志物。
人绒毛膜促性腺激素(HCG)1930年(Zondek)
促肾上腺皮质激素(ACTH)1932年(Cushing)
酶与同工酶1959年(Market)
甲胎蛋白 1963年(Abelev)
癌胚抗原 1965年(Freeman)
杂交瘤技术 1975年(Koler; Milstein)
提出肿瘤标志(Tumour Marker), 于1978年召开在美国NCI召开的人类免疫及肿瘤免疫诊断会上由Herberman提出。
癌基因 1980年(Cooper Weinbery;Bishop)
Alpha-fetoprotein (甲胎蛋白、AFP)
? AFP levels are higher in two-thirds of patients with hepatocellular cancer (cancer starting in the liver). Normal levels are less than 20 ng/ml (nanogram/ml).(约2/3原发性肝癌患者血清中AFP升高，正常人群一般不超过20ng/ml)
? The level increases with the size of the tumor. In small tumors, levels may be less than 20. (AFP浓度与肿瘤大小有关，当肿瘤太小时，可在正常范围内)
? AFP is also elevated in acute and chronic hepatitis but seldom above 100 ng/ml. (急慢性肝炎患者AFP可升高，但很少超过100)
? It is also higher in testicular cancers of the embryonal cell and endodermal sinus types and is used for follow-up of these cancers. (在胚胎细胞和内胚层细胞型睾丸癌患者中AFP也可升高，可用于此类癌症的随访)
? Elevated AFP levels are also seen in a certain type of ovarian and testicular cancer called yolk sac tumor or mixed germ cell cancer. These account for about 5% of all ovarian cancers. (某些卵黄囊肿瘤和生殖细胞癌时AFP也可升高，这些癌症约占卵巢癌的5%)
Beta-2-microglobulin (B2M) (?2微球蛋白)
? B2M levels are elevated in multiple myeloma and some lymphomas. It is very useful in determining prognosis (long-term outlook for survival). (多发性骨髓瘤和一些淋巴瘤患者血液中B2M升高，对于评价预后有重要价值)
? Patients with levels over 3 ng/ml have a poorer prognosis. (当患者血清B2M水平超过3ng/ml时、预后不良)
Bladder tumor antigen (BTA)(膀胱肿瘤抗原)
? BTA is present in the urine of many patients with bladder cancer. It is being used along with NMP22 (see below) to test patients for recurrent cancer. (膀胱癌患者尿液中出现BTA，它可单独或与NMP22联合用于监测癌症的复法)
? It is not widely used, but is still being studied. (此项目尚处于研究阶段，尚未广泛用于临床)
? It is still not certain whether it is as sensitive as cystoscopy. Most experts recommend cystoscopy as the best procedure for diagnosis and follow-up of bladder cancer. (目前尚难以确定此项目的灵敏度是否优于膀胱镜，因此临床上一般仍应用膀胱镜诊断和随访膀胱癌患者)
CA 15-3
? CA 15-3 is used primarily in patients with breast cancer. It is elevated in less than 10% of patients with early disease and in about 75% of patients with disease through their body. (CA15-3主要用于乳腺癌的辅助诊断，但早期患者仅有10%患者升高，但中晚期可有75%患者CA15-3升高)
? The normal level is around 35 U/ml (units/milliliter). Levels as high as 100 U/ml can sometimes be seen in women who do not have cancer. This marker can also be higher in other cancers. (正常人群一般在35U/ml以下，但也发现一些正常女性可高达100 U/ml。此外其它癌症患者该项目也可升高)
CA 27.29
? CA 27.29 is also used for patients with breast cancer. Although a newer test than CA 15-3, it does not appear to be any better in detecting either early or advanced disease. ( CA 27.29 主要用于辅助诊断乳腺癌，虽然该项目较新，但尚无证据表明它优于CA15-3)
? It may be less likely to be positive in people without cancer. The normal level is usually less than 38-40 U/ml, depending on the testing laboratory. Also this test measures the same marker as the CA 15-3 test, but in a different way. This marker can also be elevated in other cancers. (非癌症患者，一般该项目不会升高。正常人群一般低于38-40 U/ml，虽然此项目与CA15-3测定的是同一种标志物，但可相互补充。其它癌症患者也有可能升高)
CA 125
? CA 125 is the standard tumor marker for epithelial ovarian cancer (the most common type of ovarian cancer). (CA125是常见的上皮型卵巢癌的标准肿瘤标志物)
? More than 90% of patients have levels above 30 U/ml when the cancer is advanced. Levels are often elevated when the disease is confined to the ovary. Because of this, CA 125 is being studied as a screening test. (在癌症中晚期，有90%以上患者CA125可高于正常，且常常疾病定位于卵巢，鉴于此目前CA125作为候选筛查实验正在开展临床研究)......（后略) ......
肿瘤生物标志物的
临床应用原则
什么是"癌症"
The term 'cancer' refers to a disparate group of malignant diseases that have one thing in common: uncontrolled division of the cells of an organ or tissue. A mass of cancer cells is known as a tumour. The uncontrolled growth of a tumour results in destruction of surrounding healthy tissue. Spread of tumour cells via the blood or lymphatic system can lead to the formation of secondary growths, or metastases, in other organs or tissues.
肿瘤严重威胁人类健康和生命
? 全球因癌症每年死亡人数约600万
? 我国因癌症死亡数每年约130万
? 按目前趋势预测在2020年随全球人口达80亿，将有2000万新发癌症病人，每年死亡人数达1200万。
? 所以肿瘤的早期发现和早期诊断对肿瘤的预防和治疗至关重要。
NCI年度报告
? Americans' risk of getting and dying from cancer continues to decline and survival rates for many cancers continue to improve. The "Annual Report to the Nation on the Status of Cancer, 1975-2001".
? cancer incidence rates dropped 0.5 percent per year from 1991 to 2001,?Death rates from all cancers combined dropped 1.1 percent per year from 1993 to 2001.
? According to the report's authors, the new data reflect progress in prevention, early detection, and treatment.
定义
中华医学会检验医学分会肿瘤标志物专家委员会，中华检验医学杂志 2004；27(6)：393
? 肿瘤标志物(TM)是指在恶性肿瘤发生和增殖过程中，由肿瘤细胞的基因表达而合成分泌的或是由机体对肿瘤反应而异常产生和/或升高的，反映肿瘤存在和生长的一类物质，包括蛋白质、激素、酶(同工酶)、多胺及癌基因产物等。TM存在于病人的血液、体液、细胞或组织中，可用生物化学、免疫学及分子生物学等方法测定，且对肿瘤的辅助诊断、鉴别诊断、观察疗效、监测复法以及预后评价具有一定的价值。
ACS 定义
? Tumor markers are substances produced by cancer cells and sometimes normal cells. They can be found in large amounts in the blood or urine of some patients with cancer. Less often, they can also be found in large amounts in the blood or urine of people who do not have cancer.
理想的肿瘤指标
? 高特异性
? 高灵敏度
? 组织特异性
? 与肿瘤分型和病程有关
? 与预后相关
? 可靠的检测值
癌症的发生与发展过程
? 起动(initiation)
? 促动(promotion)
? 转化(conversion)
? 进展(progression)
肿瘤标志物分类
> 胚胎性，如AFP、CEA等
> 糖类抗原，如CA19-9、CA72-4
> 酶类，如ACP、同工酶等
> 激素类，如hCG、甲状旁腺素等
> 蛋白类，如Bence Jones 蛋白
> 基因类，包括促癌基因、抑癌基因等
检测方法
六十年代RIA
七十年代ELISA
八十年代FIA/CL/CL Enh.
九十年代 ECL
目前Bio-Chips
第一个肿瘤标志物可追溯到1846年由H Bence-Jones所证实的本周氏蛋白(Bence Jones Protein)，150余年后的今天，人们已先后发现了数十种对恶性肿瘤具有一定辅助诊断价值的肿瘤标志物。
人绒毛膜促性腺激素(HCG)1930年(Zondek)
促肾上腺皮质激素(ACTH)1932年(Cushing)
酶与同工酶1959年(Market)
甲胎蛋白 1963年(Abelev)
癌胚抗原 1965年(Freeman)
杂交瘤技术 1975年(Koler; Milstein)
提出肿瘤标志(Tumour Marker), 于1978年召开在美国NCI召开的人类免疫及肿瘤免疫诊断会上由Herberman提出。
癌基因 1980年(Cooper Weinbery;Bishop)
Alpha-fetoprotein (甲胎蛋白、AFP)
? AFP levels are higher in two-thirds of patients with hepatocellular cancer (cancer starting in the liver). Normal levels are less than 20 ng/ml (nanogram/ml).(约2/3原发性肝癌患者血清中AFP升高，正常人群一般不超过20ng/ml)
? The level increases with the size of the tumor. In small tumors, levels may be less than 20. (AFP浓度与肿瘤大小有关，当肿瘤太小时，可在正常范围内)
? AFP is also elevated in acute and chronic hepatitis but seldom above 100 ng/ml. (急慢性肝炎患者AFP可升高，但很少超过100)
? It is also higher in testicular cancers of the embryonal cell and endodermal sinus types and is used for follow-up of these cancers. (在胚胎细胞和内胚层细胞型睾丸癌患者中AFP也可升高，可用于此类癌症的随访)
? Elevated AFP levels are also seen in a certain type of ovarian and testicular cancer called yolk sac tumor or mixed germ cell cancer. These account for about 5% of all ovarian cancers. (某些卵黄囊肿瘤和生殖细胞癌时AFP也可升高，这些癌症约占卵巢癌的5%)
Beta-2-microglobulin (B2M) (?2微球蛋白)
? B2M levels are elevated in multiple myeloma and some lymphomas. It is very useful in determining prognosis (long-term outlook for survival). (多发性骨髓瘤和一些淋巴瘤患者血液中B2M升高，对于评价预后有重要价值)
? Patients with levels over 3 ng/ml have a poorer prognosis. (当患者血清B2M水平超过3ng/ml时、预后不良)
Bladder tumor antigen (BTA)(膀胱肿瘤抗原)
? BTA is present in the urine of many patients with bladder cancer. It is being used along with NMP22 (see below) to test patients for recurrent cancer. (膀胱癌患者尿液中出现BTA，它可单独或与NMP22联合用于监测癌症的复法)
? It is not widely used, but is still being studied. (此项目尚处于研究阶段，尚未广泛用于临床)
? It is still not certain whether it is as sensitive as cystoscopy. Most experts recommend cystoscopy as the best procedure for diagnosis and follow-up of bladder cancer. (目前尚难以确定此项目的灵敏度是否优于膀胱镜，因此临床上一般仍应用膀胱镜诊断和随访膀胱癌患者)
CA 15-3
? CA 15-3 is used primarily in patients with breast cancer. It is elevated in less than 10% of patients with early disease and in about 75% of patients with disease through their body. (CA15-3主要用于乳腺癌的辅助诊断，但早期患者仅有10%患者升高，但中晚期可有75%患者CA15-3升高)
? The normal level is around 35 U/ml (units/milliliter). Levels as high as 100 U/ml can sometimes be seen in women who do not have cancer. This marker can also be higher in other cancers. (正常人群一般在35U/ml以下，但也发现一些正常女性可高达100 U/ml。此外其它癌症患者该项目也可升高)
CA 27.29
? CA 27.29 is also used for patients with breast cancer. Although a newer test than CA 15-3, it does not appear to be any better in detecting either early or advanced disease. ( CA 27.29 主要用于辅助诊断乳腺癌，虽然该项目较新，但尚无证据表明它优于CA15-3)
? It may be less likely to be positive in people without cancer. The normal level is usually less than 38-40 U/ml, depending on the testing laboratory. Also this test measures the same marker as the CA 15-3 test, but in a different way. This marker can also be elevated in other cancers. (非癌症患者，一般该项目不会升高。正常人群一般低于38-40 U/ml，虽然此项目与CA15-3测定的是同一种标志物，但可相互补充。其它癌症患者也有可能升高)
CA 125
? CA 125 is the standard tumor marker for epithelial ovarian cancer (the most common type of ovarian cancer). (CA125是常见的上皮型卵巢癌的标准肿瘤标志物)
? More than 90% of patients have levels above 30 U/ml when the cancer is advanced. Levels are often elevated when the disease is confined to the ovary. Because of this, CA 125 is being studied as a screening test. (在癌症中晚期，有90%以上患者CA125可高于正常，且常常疾病定位于卵巢，鉴于此目前CA125作为候选筛查实验正在开展临床研究)......（后略) ......
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