癌胚抗原在结直肠癌淋巴结微转移检测中的应用

目的 探讨Ⅰ和Ⅱ期结直肠癌术后病理因素及淋巴结微转移对术后5年无瘤生存率的影响.方法 Ⅰ和Ⅱ期结直肠癌患者共126例,均行结直肠癌根治术.每例结直肠癌患者的淋巴结数平均为16枚(10～28枚),用癌胚抗原(CEA)指标对所有淋巴结进行免疫组化染色.统计分析临床病理因素及微转移对术后5年无瘤生存率的影响.结果 术后平均随访64.11(64～106)个月.淋巴管侵犯和肿瘤侵袭深度与淋巴结的CEA表达呈正相关,而其他临床病理因素与淋巴结CEA表达无明显相关性.10项临床病理因素对5年无瘤生存率的影响差异均无统计学意义(P＞0.05).淋巴结CEA表达阴性、孤立肿瘤细胞巢和微转移患者的5年无瘤生存率分别为75.4%、68.2%和46.2%.孤立肿瘤细胞巢患者与CEA阴性患者5年无瘤生存率比较差异无统计学意义(P=0.245).微转移患者与CEA阴性患者比较,前者5年无瘤生存率明显较低(P=0.003).结论 对于Ⅰ和Ⅱ期结直肠癌,若淋巴结中检测到微转移,其预后较差,术后复发率较高,应予以积极的术后辅助化学治疗.     

Faecal carcinoembryonic antigen in colorectal cancer patients.

Carcinoembryonic antigen (CEA) has been measured in the faeces of large bowel cancer patients and control subjects to determine whether this measurement might be a useful aid in the diagnosis of large bowel cancer. The mean faecal CEA in 24 cancer patients fell significantly from 10.43 +/- 2.39 micrograms/g pre-operatively to 3.61 +/- 0.72 micrograms/g postoperatively (p less than 0.05). Pre-operative values were not related to either tumour stage or serum CEA. In 20 patients with no known colorectal disease the mean faecal CEA was 5.43 +/- 1.95 micrograms/g which was significantly lower than the mean pre-operative value in the cancer patients (p less than 0.05). In 14 patients with a variety of benign colonic diseases the mean faecal CEA was 7.12 +/- 1.39 micrograms/g which was not significantly different from the mean pre-operative value in the cancer patients. Considerable overlap of values was observed between individual cancer and control patients making the test, as presently carried out, non-discriminatory. If the potential for making the test more cancer specific can be realised, however, faecal CEA determination may permit discrimination between cancer and non-cancer patients at a relatively early stage of disease.     

Usefulness of carcinoembryonic antigen measurement in feces of patients with colorectal cancer

Anticarcinoembryonic antigen (CEA) antisera which showed no reactions with normal adult feces were prepared in guinea pigs. Using these, levels of CEA in feces from patients with colorectal carcinoma were measured by gel diffusion and rocket immunoelectrophoresis. Sixteen of 22 (73 percent) patients with carcinoma of the colon or rectum (Dukes' A4/6, B6/8, C6/7, D0/1) had detectable CEA in their feces, while none was detected in the feces of four patients with gastric ulcers or in those of 22 normal volunteers. Five of the 16 fecal CEA-positive patients showed no elevation of plasma CEA levels. Measurements using a commercial CEA kit (Abbott Laboratories) could not detect the differences between fecal CEA values of patients with colorectal carcinoma and benign diseases, or those of normal volunteers. These results suggest that measurement of fecal CEA by specific anti-CEA antisera will be valuable in screening and diagnosis of colorectal carcinoma.     

Factors predicting long-term survival in colorectal cancer patients with a normal preoperative serum level of carcinoembryonic antigen

Purpose

The aim of this study was to determine which clinicopathological factors influenced the long-term survival after potentially curative resection of colorectal cancer patients with a normal preoperative serum level of carcinoembryonic antigen (CEA).

Methods

A total of 1,732 patients who underwent curative surgery for primary nonmetastatic colorectal cancers from 1997 to 2009 were analyzed. Of these patients, 1,128 (65.1 %) had normal level of preoperative CEA (<5 ng/mL). The predicting factors for survival were analyzed.

Results

When the serum CEA cutoff value was set at 2.4 ng/mL (median value), the high CEA groups displayed a higher percentage of older patients, males, large-diameter tumors, advanced T and N categories, and positive perineural invasion, compared to the low CEA groups. Multivariate analysis revealed that age, T category, N category, number of lymph nodes retrieved, operative method, lymphovascular invasion, perineural invasion, postoperative chemotherapy, and preoperative serum CEA level ≥ 2.4 ng/mL were independent predictors for 5-year overall survival, while tumor location, tumor size, T category, N category, lymphovascular invasion, and perineural invasion were independent predictors for 5-year disease-free survival.

Conclusions

Even if patients with colorectal cancer have a normal preoperative CEA before surgery, CEA may be useful for prognostic stratification using 2.4 ng/mL as the cutoff.     

Diagnostic value of carcinoembryonic antigen combined with cytokines in serum of patients with colorectal cancer

In clinical practice, colorectal cancer (CRC) is difficult to distinguish from ulcerative colitis and colon polyps. Practical markers are useful for diagnosing and treating patients with CRC. Carcinoembryonic antigen (CEA) is a biomarker for diagnosing patients with CRC. However, the diagnostic sensitivity and specificity of CEA are not high. Interleukin (IL)-10, IL-17A, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and transforming growth factor beta (TGF-β) are assumed to be closely related to the occurrence and development of human cancer. Some have been used as diagnostic markers in CRC. It remains unclear whether cytokines in combination with CEA could be used as biomarkers for the diagnosis of CRC. Serum levels of IL-10, IL-17, TNF-α, IFN-γ, and TGF-β in patients with CRC, ulcerative colitis, colonic polyps, stomach cancer, and healthy controls were measured by enzyme-linked immunosorbent assay. The serum level of CEA was detected using electrochemiluminescence. The value of the cytokines combined with CEA as a biomarker panel for the diagnosis of CRC was assessed. CEA, IL-10, IL-17A, TNF-α, and TGF-β levels were significantly increased in CRC. CEA displayed a higher specificity than the other cytokines. IL-17A, TNF-α, and TGF-β displayed higher sensitivities than CEA, IL-10, and IFN-γ in the diagnosis of CRC. The combination of serum CEA, IL-17A, and TNF-α achieved higher diagnostic efficacy for CRC (area under the curve = 0.935). The combination of CEA, IL-17, and TNF-α has better diagnostic efficacy than CEA alone in CRC. A panel containing IL-17A, TNF-α, and CEA could be a promising molecular biomarker panel to diagnostically differentiate CRC from ulcerative colitis, colon polyps, and stomach cancer.     

Serial plasma carcinoembryonic antigen measurements in the management of metastatic colorectal carcinoma

Serial carcinoembryonic antigen (CEA) measurements were evaluated in a group of 263 patients undergoing systemic chemotherapy for metastatic colorectal carcinoma. Initial CEA levels were not found to be of value in predicting the likelihood of subsequent tumor response. Although a general relation between serial CEA measurements and clinical tumor measurements was noted, these measurements were discordant in a substantial proportion of patients. Tumor measurements as an index of response to therapy were strongly correlated with survival, whereas changes in CEA values and patient survival were not correlated at a statistically significant level. Serial CEA measurements were perhaps of some value in predicting progression of malignant disease, and were roughly comparable to serum alkaline phosphatase assay in assessing response of liver metastasis to chemotherapy. Overall, serial CEA measurements added little to the standard clinical assessment of patients with advanced colorectal carcinoma receiving chemotherapy.     

Value of carcinoembryonic antigen in the management of colorectal cancer

PURPOSE: The practical value of carcinoembryonic antigen (CEA) assay in the management of colorectal cancer after surgery is controversial. The value of CEA in the management of colorectal cancer was reviewed and discussed to justify the use of CEA assay in the management of colorectal cancer. METHODS: A retrospective study was performed on 318 patients who underwent resection by one surgeon (JYW) between 1981 and 1986 and who were followed for a minimum of 5 years or until death. RESULTS: The incidence of preoperative CEA levels >5 ng/ml in Dukes Stages A, B, C, and D were 0, 32, 48, and 79 percent, respectively. Five-year survival rates for groups with CEA levels 5 ng/ml and >5 ng/ml were 85 percent and 55 percent (P < 0.05), respectively, in Dukes Stage B patients and 64 percent and 37 percent (P < 0.05) in Stage C patients. The sensitivity and specificity of postoperative CEA monitoring in detecting recurrent diseases were 66 percent and 94 percent, respectively, for patients with a preoperative CEA value 5 ng/ml and 97 percent and 88 percent for patients with a higher preoperative CEA value. CONCLUSION: CEA is still the best tumor marker available to be used as an independent prognostic factor and as a monitor for recurrence of disease after primary tumor resection.     

Studies on effect of carcinoembryonic antigen on leucocyte migration inhibition test in patients with colorectal cancer

Leucocyte migration inhibition test (LMIT) is a useful method to detect tumor associated antigens (TAA) in cancer patients. Carcinoembryonic antigen (CEA) is one of the best tumor markers for gastrointestinal cancer, and especially for colorectal cancer patients, who show high plasma CEA level frequently. In this study, we performed LMIT in 71 colorectal cancer patients with 3 M KCl extracts of cancer tissues and measured concentration of CEA in the plasma and the extracts of cancer tissue simultaneously. Although CEA in colorectal cancer extracts was individually varied from low to high in concentration, the levels of CEA had no relation to LMI reactivity. In addition, the LMI reactivity of colorectal cancer patients did not relate to the plasma CEA level of the corresponding patient. The results suggest that some antigens which induce leucocyte migration inhibition factor (LMIF) to lymphocytes from colorectal cancer patients might be different substances from CEA.     

癌胚抗原阳性的结直肠癌患者微小核糖核酸表达谱的初步研究

目的 探讨血清癌胚抗原(CEA)阳性结直肠癌患者微小核糖核酸(miRNA)表达谱的改变.方法 选取6例结直肠癌患者的冰冻组织标本,其中3例血清CEA水平高于正常.提取肿瘤组织标本的miRNA,用荧光染料Cy3标记,并与Agilent miRNA寡核苷酸基因芯片杂交.用扫描仪扫描荧光信号,并用Feature Extraction软件分析处理扫描结果,初步研究CEA阳性结直肠癌miRNA表达谱.为了验证微阵列表达谱的结果,选择miR-143行实时定量RT-PCR.结果 CEA 阳性与阴性结直肠癌相比,11个miRNA出现表达差异,其中hsa-miR-125a-3p、hsa-miR-134、hsa-miR-224、hsa-miR-574-5p、hsa-miR-575表达上调,hsa-miR-1、lisa-miR-143、hsa-miR-143*、hsa-miR-21、hsa-miR-23a、hsa-miR-27a表达下调,712个miRNA无明显表达差异.实时定量RT-PCR结果显示,miR-143在CEA阳性的结直肠癌组织中表达下降明显,低于CEA阴性结直肠癌组织,与miRNA微阵列检测结果一致.结论 CEA阳性与阴性结直肠癌相比,具有不同的miRNA表达谱,这为结直肠癌的分子分型与个性化治疗提供了理论基础.     

Role of carcinoembryonic antigen in predicting resectability of recurrent colorectal cancer

The reported low resectability rate for patients with recurrent colorectal cancer who have carcinoembryonic antigen (CEA) levels >11 has led us to perform this study. One hundred twenty-four patients who underwent Radioimmunoguided Surgery ^® (RIGS ^®)procedures for recurrent colorectal cancer from 1986 to the present were studied. In surgery, all patients underwent a traditional exploration followed by survey with a hand-held, gamma-detecting probe to detect preinjected radiolabeled monoclonal antibodies attached to cancer cells. Sites of metastases included: 72 liver (58.1 percent), 23 pelvis (18.5 percent), 15 distant lymph nodes (12.1 percent), 2 anastomotic (1.6 percent), and 12 other sites (9.7 percent). The resectability rate was 43.5 percent (54 patients). The mean preoperative CEA level for patients with resectable disease was significantly lower than for patients with unresectable disease (P=0.017): unresectable—mean, 87.1; SD, 141.0; minimum, 0.3; maximum, 501; resectable—mean, 36.6; SD, 59.3; minimum, 0.3; maximum, 329. The CEA level for patients with liver metastasis did not vary significantly from those patients without metastasis: 70 vs. 58.2 (P=0.58). Those patients with resectable liver tumors had lower mean CEA levels than those with unresectable liver, approaching significance: 41.6 vs. 91.9 (P=0.065). Other metastatic sites had a mean CEA level of: pelvic, 72.6; distant lymph nodes, 47.8; anastomotic, 2.7; and other sites, 53.8. These data suggest that there is a significant difference between the preoperative CEA level of the resectable and unresectable recurrent colorectal cancer patients, but the large standard deviation does not justify abandonment of exploration for any CEA level.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Francisco, California, June 7 to 12, 1992.     

Carcinoembryonic antigen in monitoring of response to systemic chemotherapy in patients with metastatic colorectal cancer

The response to chemotherapy of solid tumors is generally assessed by measuring tumors visualized by imaging. However, the response assessment based on imaging is not always feasible because patients often have disease not measurable by imaging, such as diffuse peritoneal dissemination. We evaluated the correlation between the change on imaging and change in CEA levels for assessing chemotherapeutic response of patients with metastatic colorectal cancer. Between July 1993 and August 1999 we retrospectively examined 136 patients with metastatic colorectal carcinoma, all of whom had measurable lesions. Forty patients received oral tegafur-uracil (300 mg/m2/day) plus folinic acid (60 mg/day) for 4 weeks, repeated every 5 weeks, as the firstline treatment. Another 96 patients received either a weekly intravenous bolus injection of 5-fluorouracil (400 mg/m2) plus folinic acid (20 mg/m2), or an intravenous bolus injection of 5-fluorouracil (425 mg/m2) plus folinic acid (20 mg/m2) for 5 consecutive days every month. Responders, based on CEA assessment, were defined as those with a greater than 50% drop in CEA level for more than 4 weeks. The pretreatment CEA levels were elevated beyond the normal cutoff value in 110 (81%) patients. A response rate of 18.4% (95% CI, 11.9-24.9%), including 8 complete remissions and 17 partial remissions, was achieved according to imaging studies. The response rate assessed by CEA was 25% (34/136). Sixteen responders (47%) based on CEA had no remission on imaging. The sensitivity of change in CEA levels in the prediction of true responders and progressive diseases on imaging were 72% and 81%, respectively. In terms of the positive predictive value, change in CEA levels in the prediction of true responders and progressive disease on imaging were 53% and 85%, respectively. Patients with remarkable falls on CEA levels survived significantly longer than nonresponders (P < 0.001, log-rank test). At follow-up of 48 months the median survival for responders and nonresponders assessed by CEA was 28 months and 13 months, respectively. These data suggest that measurement of CEA levels might be helpful in monitoring chemotherapeutic response when imaging study is unsuitable for assessing the response in clinical practice. Furthermore, measurement of CEA levels may be helpful in determining the prognosis of patients with metastatic colorectal cancer receiving chemotherapy.     

Prognostic value of carcinoembryonic antigen level in rectal cancer treated with neoadjuvant chemoradiotherapy

Background  The purpose of this study was to identify clinical and pathological parameters to improve prediction of disease-free survival (DFS) and overall survival (OS) in patients treated with neoadjuvant chemoradiotherapy for rectal cancer. Methods  Between July 1995 and May 2007, 148 patients with primary rectal adenocarcinoma received neoadjuvant chemoradiotherapy followed by mesorectal excision. Preoperative treatment included various protocols, UFT and leucovorin (28%) and oxaliplatin-based chemotherapy (72%). Clinical and pathological variables were evaluated in relation to patient outcomes. Results  Thirteen percent of patients achieved a complete pathologic response. No response or minimal response as defined by Dworak (Tumor Regression Grade 0/1) was observed in 30 patients (20%). At a median follow-up of 37 months, the 3-year DFS and OS were 64% and 83%, respectively. Pre-treatment serum carcinoembryonic antigen (CEA) level ≤ 2.5 ng/ml was associated with higher DFS (74 vs. 53%; p = 0.018), higher complete pathologic responses (21 vs. 9%; p = 0.05), and less recurrences (24 vs. 44%; p = 0.014). Conclusion  The data suggest that a CEA level ≤ 2.5 ng/ml might be a predictor not only of tumor response, as has been suggested before, but also of DFS. This finding could be useful in the future to predict individual risk and to develop more aggressive or alternative strategies. Supported in part by Biomedical Research Foundation, University Hospital La Paz. All authors have no financial disclosures.     

The usefulness of CA15.3, mucin-like carcinoma-associated antigen and carcinoembryonic antigen in determining the clinical course in patients with metastatic breast cancer

Levels of mucin-like carcinoma-associated antigen (MCA), CA15.3 and carcinoembryonic antigen (CEA) were measured in consecutive serum samples of 40 women with metastatic breast cancer. A change in antigen level of more than 25%, either an increase or a decrease, was considered to predict progressive or responsive disease respectively. A change of less than 25% was considered to predict stable disease. MCA, CA15.3 and CEA were elevated in the serum of 68%, 76% and 48% of the patients respectively (P<0.05). The overall prediction of clinical course was similar for all three markers. A more than 25% increase of MCA, CA15.3, and CEA was observed in 61%, 54% and 36% respectively. The predictive value of a more than 25% increase was high for all three markers: 94%, 94%, 83%. Changes in marker levels were correlated with each other. Logistic regression analysis showed that combining MCA and CA15.3 did not improve the prediction further. In conclusion, these tumour markers may help in evaluating the disease course and there is no advantage in combining MCA and CA15.3.     

Bile carcinoembryonic antigen levels and occult hepatic metastases from colorectal cancer

PURPOSE: Up to 30 percent of patients will have occult hepatic metastases at the time of curative surgery for colorectal cancer. The ability to predict this group of patients would allow better targeting of appropriate therapy. It has been shown previously that patients with overt hepatic metastases have significantly high levels of carcinoembryonic antigen in gallbladder bile compared with serum levels. The aim of this study was to assess the accuracy of bile carcinoembryonic antigen levels taken at the time of operation in predicting patients with occult hepatic metastases. METHODS: Bile and serum carcinoembryonic antigen samples were collected from 37 patients undergoing surgery for colorectal cancer, 26 of whose procedures were deemed curative and who were followed up for a median of 63.5 months. RESULTS: Twelve patients were alive with no evidence of recurrent disease, and two had recurrent disease, whereas 12 died of disease. The median (interquartile range) serum carcinoembryonic antigen in the disease-free group was 2.8 (1.1–6.1) ng/ml, and in the recurrent group it was 6.35 (4.3–30) ng/ml (P=0.006), whereas bile carcinoembryonic antigen in the disease-free group was 7 (5–39) ng/ml as compared with 31 (5–383.7) ng/ml in the recurrent group (P=0.210). The accuracy of serum carcinoembryonic antigen in predicting occult hepatic metastases was 77 percent compared with 72 percent for bile carcinoembryonic antigen. CONCLUSION: Intraoperative bile carcinoembryonic antigen levels are no more accurate than serum carcinoembryonic antigen levels in predicting occult hepatic metastases in patients undergoing potentially curative colorectal cancer surgery.Supported by a grant from The Scottish Home and Health Department.     

Prognostic impact of carcinoembryonic antigen (CEA) on patients with metastatic pancreatic cancer: A retrospective cohort study

BackgroundCarcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its level is increased in 30–60% of patients with pancreatic cancer (PC). However, little is known about the implications of CEA as a prognostic marker in metastatic PC. The purpose of this study was to examine the usefulness of CEA levels as a prognostic marker in patients with metastatic PC.MethodsWe conducted a retrospective cohort study using data from a computerized database. A total of 433 patients with metastatic disease were analyzed.ResultsMedian overall survival (OS) was significantly shorter for patients with high CEA (>5 ng/ml) than with normal CEA (≤5 ng/ml) (6.8 vs. 10.3 months, respectively; p < 0.001). After adjustment, CEA level was an independent predictive factor for OS (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.45–2.26). In the high CEA group, OS in patients treated with combination chemotherapy was similar to that with single-agent chemotherapy (median, 7.1 vs. 6.8 months; HR for OS, 0.99; 95% CI, 0.71–1.40).ConclusionsThe present results show that CEA level is an independent prognostic factor in patients with metastatic PC. A combination chemotherapy regimen may offer modest survival benefit in patients with high CEA.     

Value of 18F-FDG PET-CT in surveillance of postoperative colorectal cancer patients with various carcinoembryonic antigen concentrations

AIM:To evaluate the value of positron emission tomography(PET)/computerized tomography(CT)in surveillance of colorectal cancer(CRC)patients with different carcinoembryonic antigen(CEA)concentrations.METHODS:One hundred and six postoperative CRC patients who had suspected recurrence or metastasis and received fluorodeoxyglucose(FDG)PET/CT within one week were included in this study.The final diagnosis was confirmed by histological examination or clinicalfollow-up over at least six months.RESULTS:The sensitivity,specificity,and accuracy of FDG PET/CT were 95.2%,82.6%,and 92.5%,and94.8%,81.4%and 92.8%,respectively,in the caseand lesion-based analyses.The sensitivity and accuracy of FDG PET/CT significantly differed from CT in both analyses(χ2=8.186,P=0.004;χ2=6.201,P=0.013;χ2=13.445,P=0.000;χ2=11.194,P=0.001).In the lesion-based analysis,the sensitivity,specificity,and accuracy of FDG PET/CT in the abnormal CEA group were97.8%,82.6%,and 95.6%,compared with 81.3%,80%,and 80.6%for patients with normal CEA levels.In case-based analysis,the sensitivity,specificity,and accuracy of FDG PET/CT were 97.2%,77.8%,and 95%in abnormal CEA group.Only in lesion-based analysis,the sensitivity and accuracy of FDG PET/CT in the abnormal CEA group were significantly superior to those in the normal CEA group(χ2=6.432,P=0.011;χ2=7.837,P=0.005).FDG PET/CT changed the management in 45.8%of patients with positive scans.CONCLUSION:FDG PET/CT showed superior diagnostic value and is an advisable option in surveillance of postoperative CRC patients with a vague diagnosis.