hMAM mRNA和CEA mRNA RT-PCR检测乳腺癌外周血微转移

目的:应用RT-PCR法检测乳腺癌患者外周血中的hMAM mRNA和CEA mRNA表达情况.方法:用RT-PCR法,检测52例乳腺癌患者外周血中hMAM mRNA和CEA mRNA的表达情况,另抽取28例乳腺良性疾病患者和10例健康志愿者外周血标本作为对照.结果:52例乳腺癌患者外周血中hMAM mRNA和CEA mRNA的阳性率分别为30.8%、34.6%.28倒乳腺良性疾病患者和10例健康志愿者外周血中hMAM mRNA、CEA mRNA表达均为阴性.二者的阳性表达与患者的腋淋巴结状况、TNM分期差异均有显著性意义(P＜0.05),而与患者的年龄、原发肿瘤大小、病理类型以及激素受体状况等差异均无显著性(P＞0.05).结论:hMAM mRNA、CEA mRNA均可作为标志物来检测乳腺癌患者外周血中微转移,联合检测可增加外周血中循环肿瘤细胞的检出率.     

A re-evaluation of carcinoembryonic antigen (CEA) as a serum marker for breast cancer: a prospective longitudinal study.

PURPOSE: Carcinoembryonic antigen (CEA) is still a widely used test for monitoring breast cancer, although recent reports discourage its routine use because of low sensitivity. This is a prospective study evaluating the efficacy of CEA and CA 15.3 in monitoring breast cancer. EXPERIMENTAL DESIGN: Serum CEA and CA 15.3 were measured in 2191 patients with either benign (n = 738) or malignant (n = 1453) breast diseases. Five hundred and forty-nine patients were monitored during postsurgical follow-up for either a minimum of 5 years or until time of recurrence. Fifty-three patients with metastases were also monitored during chemotherapy. RESULTS: Elevated CEA and CA 15.3 levels were found in 16.7% and 33.0% of patients, respectively. CEA sensitivity rose to 41.3% and CA 15.3 sensitivity rose to 80.8% in metastatic patients. The adjunct of CEA increased the CA 15.3 sensitivity by 6% in the overall population and by only 2.1% for patients with metastases. During postsurgical follow-up, CEA was elevated in 38.0% and CA 15.3 in 70.2% of patients with recurrence. The combination of CEA and CA 15.3 increased the overall sensitivity by only 1.4%. Longitudinal monitoring of 53 metastatic patients undergoing chemotherapy demonstrated that, when positive, both CEA and CA 15.3 paralleled response to treatment, although CA 15.3 was a significantly more powerful marker for determining response to treatment. The cost effectiveness ratio of CEA was clearly less favorable than that of CA 15.3. CONCLUSIONS: CEA monitoring should be considered an expensive and inefficient method of follow-up evaluation for breast cancer patients, and it provides no additional value when used in combination with CA 15.3.     

hMAM RNA 和CEA RNA T-PCR检测乳腺癌外周血微转移

目的应用RT-PCR法检测乳腺癌患者外周血中的human ammaglobin(MAM)mRNA和CEA RNA表达情况.方法用RT-PCR法,检测52例乳腺癌患者外周血中hMAM RNA和CEA RNA的表达情况,另抽取28例乳腺良性疾病患者和10例健康志愿者外周血标本作为对照.结果 52例乳腺癌患者外周血中hMAM RNA和CEA RNA的阳性率分别为30.8％、34.6％.28例乳腺良性疾病患者和10例健康志愿者外周血中hMAM RNA、CEA RNA表达均为阴性.两者的阳性表达均与患者的腋淋巴结状况、TNM分期差异有显著性意义(P<0.05).而与患者的年龄、原发肿瘤大小、病理类型以及激素受体状况等均无显著性差异(P＞0.05).结论 hMAM RNA、CEA RNA均可作为标志物来检测乳腺患者外周血中微转移,联合检测可增加外周血中循环肿瘤细胞的检测率.     

Diagnostic value of mucin-like carcinoma-associated antigen (MCA) in breast cancer

The diagnostic value of mucin-like carcinoma-associated antigen (MCA) was compared to that of carcinoembryonic antigen (CEA) and/or CA 15.3 in patients with breast cancer. A total of 368 patients with breast cancer were studied, of whom 253 were free of metastases, whereas 94 had either skeletal or visceral metastases or diffuse metastatic disease. The diagnostic sensitivity of MCA proved to be comparable to that of CA 15.3 and superior to that of CEA in patients with metastatic breast cancer. In contrast, the specificity of MCA was superior to that of CA 15.3. Finally, the diagnostic sensitivity of each of the tested tumour markers, i.e. MCA, CEA and CA 15.3, could be improved by their combined use. We conclude that MCA, either alone or in combination with CA 15.3 and CEA, can improve the monitoring of disease progression in patients with metastatic breast cancer.     

hMAM mRNA在检测乳腺癌外周血微小转移中的应用

目的 探讨乳腺组织特异性基因hMAM mRNA作为检测乳腺癌血道微小转移指标的可能性。方法 采用巢式PCR结合荧光定量PCR,对63例乳腺癌患者、8例乳腺增生患者、5例乳腺纤维腺瘤患者、25例其他癌患者以及31例健康志愿者的外周血进行检测。结果63例乳腺癌患者外周血中hMAM mRNA阳性率30．2％（19／63）,手术后阴转率为31．6％（6／19）。乳腺良性疾病、胃癌、大肠癌、食管癌、肺癌、卵巢癌患者外周血中均阴性,而31例健康献血员中有1例阳性。hMAM mRNA表达随肿瘤分期进展阳性率增高,但与肿瘤分期、ER和PR状态无关（P＞0．05）。结论 hMAM mRNA特异表达于乳腺癌患者外周血,有可能作为检测乳腺癌血道微小转移的指标。     

Use of serial carcinoembryonic antigen and CA 15.3 assays in detecting relapses in breast cancer patients

Summary To evaluate the utility of CEA and CA 15.3 for early diagnosis of recurrence, serial serum determinations of both antigens were performed in 1023 patients (follow-up: 1–10 years, mean 6.2 years) with primary breast cancer (CA 15.3 in 533 cases) and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). 246 patients developed metastases during follow-up.Results: CEA and CA 15.3 were elevated (> 10 ng/ml or > 60 U/ml, respectively) prior to diagnosis in 40% (98/246) and 41% (37/91) of the patients with recurrence, with a lead time of 4.9 ± 2.2 and 4.2 ± 2.3 months, respectively. When patients with locoregional recurrences were excluded, sensitivity improved to 46% (CEA) and 54% (CA 15.3), and to 64% with both tumor markers (CEA and/or CA 15.3). Higher levels of both CEA and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse, and a higher lead time were found in ER+ (CEA) or PgR+ patients (CA 15.3) than in those that were negative for these receptors in the primary tumor (p < 0.001). Specificity of the tumor markers was 99% for both CEA (777 NED patients) and for CA 15.3 (444 NED patients), respectively. In conclusion, CEA and CA 15.3 are useful tools for early diagnosis of metastases, mainly in those patients with ER+ or PR+ tumors.     

Value of CA 15.3 in breast cancer and comparison with CEA and TPA: A study of specificity in disease-free follow-up patients and sensitivity in patients at diagnosis of the first metastasis

Summary The specificity and sensitivity of a tumor marker (TM) are important in establishing its potential clinical utility for a specific type of neoplasm. CA 15.3 is a TM specific for breast cancer; it is defined by two monoclonal antibodies (DF3 and 115D8), whose specificity, in disease-free follow-up patients, and sensitivity, in patients at diagnosis of first metastasis, have been evaluated in the present study and compared with those of carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA).Serum concentrations of all three TMs were quantified in 618 individuals: 80 healthy controls, 421 patients with local breast cancer who became free of disease following locoregional treatment, and 117 patients with disseminated disease at diagnosis of metastasis. Radioimmunoassay (RIA) was the method employed, and the cut-off values obtained were 30 U/ml for CA 15.3, 5 ng/ml for CEA, and 120 U/I for TPA. The results showed CA 15.3 and CEA specificities to be analogous (95.7 and 95.5%, respectively). TPA specificity (81.9%) was lower (p<0.001). During adjuvant therapy, CA 15.3 serum levels were seen to increase, followed by a normalization of concentration after terminating therapy. On the other hand, CA 15.3 and TPA sensitivities (64.1 and 67.5%, respectively) were greater than for CEA (44.4%, p<0.01).It is concluded that CA 15.3 is a useful TM for breast cancer, as it offers a greater sensitivity than CEA and a higher specificity than TPA. Combining CA 15.3 and CEA fails to increase CA 15.3 sensitivity, while combining CA 15.3 with TPA increases false-positives and so likewise offers no additional benefit.     

人乳腺癌外周血中hMAM mRNA表达及临床意义

目的：研究人乳腺癌外周血珠蛋白（hMAM）mRNA表达及临床意义。方法：应用nested-RT-PCR技术检测50例乳腺癌外周血hMAM mRNA的表达和化疗前后外周血hMAM mRNA的变化,并取20例乳腺纤维腺瘤、10例健康志愿者作阴性对照。结果：50例乳腺癌外周血hMAM mRNA的阳性表达率为34.0%;20例乳腺纤维腺瘤及10例健康志愿者外周血中均未检出hMAM mRNA的表达。hMAM mRNA的阳性与淋巴结转移状况、肿瘤TNM分期之间差异有统计学意义;50例乳腺癌化疗前检测17例hMAM mRNA阳性,化疗2～3周期后13例hMAM mRNA转为阴性,转阴率76.5%（13/17）,化疗前后差异非常显著（P=0.001）。结论：乳腺癌外周血中hMAM mRNA表达可以反映术后化疗对乳腺癌血液微转移的影响,有望成为乳腺癌血道微转移标志物和一个重要的预后指标。     

乳腺癌患者骨髓中人乳腺珠蛋白mRNA的检测及其临床意义

目的探讨乳腺癌患者骨髓中人乳腺珠蛋白（hMAM）mRNA的表达及其临床意义。方法应用巢式RT—PCR技术,同时检测75例乳腺癌患者、15例乳腺良性病变患者和8例健康人骨髓中hMAMmRNA的表达,分析hMAMmRNA表达与临床病理因素、Ki67、p53和血管内皮生长因子（VEGF）的关系。结果RT—PCR检测的敏感度达到10^-6。75例乳腺癌患者中,21例检测出hMAMmRNA阳性表达,阳性表达率为28．0％。hMAMmRNA阳性表达与乳腺癌腋窝淋巴结转移和PR状况有关（P〈0．05）,与年龄、肿瘤大小、临床分期和ER状况无关（P〉0．05）;与乳腺癌组织Ki67表达呈正相关（X^2=4．936,P=0．026）。乳腺良性病变患者和健康人骨髓中,未检测到hMAMmRNA表达。结论应用RT—PCR方法检测乳腺癌骨髓中hMAMmRNA的表达,敏感度高、特异性好。hMAMmRNA可作为检测乳腺癌患者骨髓中播散肿瘤细胞的分子指标之一,可为乳腺癌患者的治疗和预后判断提供帮助。     

乳腺癌患者外周血hMAM及SBEM检测及其临床意义

目的研究乳腺癌患者外周血人乳腺珠蛋白（hMAM）及乳腺上皮粘蛋白（SBEM）的表达及临床意义。方法应用逆转录聚合酶链反应（RT-PCR）技术检测58例乳腺癌患者外周血hMAM mRNA及SBEM mRNA的表达，并用健康志愿者及乳腺良性肿瘤患者各10例作为对照。结果hMAM及SBEM在58例乳腺癌患者外周血的阳性表达率分别为34.5%、25.9%，乳腺良性肿瘤和正常对照均无阳性表达，两者的阳性表达与患者的临床分期显著相关（P〈0.05），两者联合检测的总阳性率为41.4%（24/58），与单一标志物相比缺乏统计学意义。结论hMAM及SBEM特异性表达于乳腺癌外周血，可作为检测乳腺癌外周血肿瘤细胞标志物，并有可能在乳腺癌微转移诊断和预后判断中具有重要意义。     

SBEM和hMAM在乳腺癌中的表达及临床意义

目的 探讨乳腺上皮粘蛋白（SBEM）和人乳腺珠蛋白（hMAM）在乳腺癌中的表达及其临床意义。方法 采用实时荧光定量PCR（RT-PCR）检测109例乳腺癌患者和25例对照组（5例健康者与20例其他肿瘤患者）外周血SBEM mRNA和hMAM mRNA的表达情况,流式细胞术检测SBEM和hMAM阳性表达细胞的比例;并分析其与临床病理特征的关系。结果 RT-PCR检测显示SBEM mRNA和hMAM mRNA仅表达于乳腺癌患者外周血中,在健康者和其他肿瘤患者外周血中无表达。流式细胞术检测显示SBEM和hMAM在乳腺癌患者中阳性表达细胞的比例分别为55.9％和40.4％,而在健康者和其他肿瘤患者中仅为10％左右。乳腺癌外周血SBEM和hMAM表达与TNM分期、淋巴结转移有关,而与年龄、肿瘤大小、激素受体和C erbB-2均无关。结论 SBEM mRNA和hMAM mRNA在乳腺癌患者外周血中均有高表达,两者联合检测有助于判断血道微转移的存在。     

术前CEA和CA15-3对乳腺癌的临床应用价值

目的:探讨术前CEA和CA15-3对乳腺癌早期诊断的价值及其与临床病理因素的相关性。方法:回顾性分析2000年-2005年1028例乳腺癌患者的CEA、CA15-3水平以及与临床病理因素的关系。结果:CEA、CA15-3联合检测、CA15-3及CEA单独检测对乳腺癌的早期诊断敏感性均低,分别为20.9%、15.3%、9.5%;CA15-3和CEA联合检测在肝、骨和肺转移的阳性率则分别为86.7%、90.9%、45.5%(P=0.030),CA15-3、CEA单独检测对转移病灶的敏感性无差异(P均>0.05)。CEA、CA15-3单独检测及CEA、CA15-3联合检测的阳性率与乳腺癌的临床分期、T分期、N分期呈正相关性,(P均<0.001)。CEA单独检测的阳性率与年龄>45岁、绝经后、ER阴性、PR阴性、Her2阳性有显著相关性(P均<0.05);除CEA、CA15-3联合检测的阳性率与Her2阳性呈正相关,联合检测及CA15-3单独检测与其他因素无相关性。结论:术前CEA和CA15-3对乳腺癌的早期诊断缺乏敏感性,但可作为预测预后的重要指标。     

hMAM和CK19 mRNA联合检测早期乳腺癌循环肿瘤细胞的临床价值

目的:评价hMAM和CK19 mRNA联合检测早期乳腺癌循环肿瘤细胞的临床价值.方法:采用RT-PCR检测早期乳腺癌患者CK19、hMAM mRNA阳性循环肿瘤细胞.结果:hMAM和CK19 mRNA联合检测早期乳腺癌患者循环肿瘤细胞阳性率(52.0%)均高于良性乳腺疾病患者(16.7%)和健康体检者(5.0%), P值分别为0.004和0.000;阳性率与癌组织HER-2过表达相关,P=0.049.联合检测的敏感度为57.5%,特异度为88.6%.26例联合检测阳性患者,13例随访期出现转移复发,P=0.001;中位无瘤生存期明显降低,P=0.000.结论:hMAM和CK19 mRNA是一组敏感度和特异度较好的诊断早期乳腺癌患者循环肿瘤细胞的基因标志,可能作为早期乳腺癌术后监测转移复发辅助指标.     

hMAM mRNA表达情况与乳腺癌的关系

目的 探讨人乳腺珠蛋白(hMAM)mRNA在乳腺癌患者外周血中的表达情况及意义.方法 选取87例乳腺癌患者、70例乳腺良性肿瘤患者和50例健康志愿者,采用巢式-逆转录-聚合酶链反应检测其外周血hMAM mRNA的表达水平.结果 乳腺癌患者的外周血hMAM mRNA阳性率为54.02%,高于乳腺良性肿瘤患者的1.43%和健康志愿者的0,差异均有统计学意义(P﹤0.05);乳腺良性肿瘤患者和健康志愿者的外周血hMAM mRNA阳性率比较,差异无统计学意义(P﹥0.05).Ⅲ~Ⅳ期、有淋巴结转移的乳腺癌患者的hMAM mRNA阳性率高于Ⅰ~Ⅱ期和无淋巴结转移的患者(P﹤0.05).乳腺癌患者化疗后的外周血hMAM mRNA阳性率为18.39%,低于化疗前的54.02%(P﹤0.05).结论 乳腺癌患者外周血hMAM mRNA的阳性表达与TNM分期和淋巴结转移情况有关,可为临床诊断和预后判断提供依据.     

腋淋巴结阴性乳腺癌外周血hMAM检测意义

目的:应用乳腺癌特异性标志物乳腺珠蛋白(hMAM)检测腋淋巴结阴性乳腺癌(axillary lymph node negative breast cancer,ALNNBC)外周血中微转移,并探讨其与临床病理因素的关系.方法:采用巢式RT-PCR方法,分别检测62例ALNNBC、6例乳腺良性疾患和6例健康成人女性外周血中hMAM mRNA的表达,并以MDA-MB415细胞为阳性参考检测该方法的灵敏度.结果:ALNNBC外周血hMAM表达阳性率为32.3%(20/62),乳腺良性疾患组和健康成人女性组全部阴性表达;该方法检测外周血微转移的灵敏度达1/106;C-erbB2基因阳性表达者微转移发生率高(P＜0.01),月经状态、肿瘤大小、组织学类型、ER状态、p53表达等与微转移无关(P＞0.05);复发转移组较无瘤生存组外周血中微转移率高(P＜0.01).结论:hMAM可作为乳腺癌外周血微转移的标志物;ALNNBC微转移与C-erbB2密切相关;外周血微转移可以作为ALNNBC预后指标.