Correlation of total (TSA) and lipid and bound (LSA) sialic acid levels with cytology of cyst or body fluids in cancer patients.

In this preliminary study, aiming at the early diagnosis or the confirmation of neoplastic spreading, the levels of sialic acid (TSA and LSA, total sialic acid and "lipid bound" sialic acid) were measured and correlated with the corresponding cytologic findings in 111 body or cystic fluid samples taken from patients with suspected or confirmed cancer. The samples were classified according to the body fluid origin: peritoneal (35), breast cyst (22), pleural (21), thyroid gland cyst (5), renal cyst (5), ovarian cyst (6), bronchial washing (3), douglasic cavity (3) and various other origins (11). It was found that 32.43% of the samples were TSA positive, 44.14% LSA positive, 20.75% cytologic and 8.49% cytology suspect (positive + suspect = 29.24%). Thus, the combination of a tumor biomarker with the corresponding cytology of the body fluid gives the best possible results, as regards both the confirmation of positive cytology and the detection of possible metastases, as well as the monitoring of the disease after treatment.     

Faecal carcinoembryonic antigen (CEA) in patients with large bowel cancer

The possibility that faecal CEA may be a more useful measurement than serum CEA for the detection of large bowel cancer has received very little attention. For this reason faecal CEA was measured before and after tumour resection in colorectal cancer patients and in a variety of control subjects. CEA was extracted from faeces by a new method with 3M KCl and assayed by an EIA technique utilising two monoclonal antibodies. Mean +/- SE faecal CEA in 32 cancer patients was 4.15 +/- 1.17 micrograms/g preoperatively. Values were not related to either stage of disease or serum CEA and they fell to 0.83 +/- 0.34 micrograms/g (n = 20) following tumour resection (P less than 0.05). Mean +/- SE faecal CEA in 34 control patients with no known colorectal disease was 0.94 +/- 0.49 micrograms/g which was significantly lower than in the cancer patients (P less than 0.05). Furthermore faecal CEA in 25 patients with non malignant colorectal disease was 1.44 +/- 0.63 micrograms/g which again was significantly lower than that in the cancer patients. It is concluded that as CEA is present in the faeces of the majority of colorectal cancer patients even at early stages of the disease its measurement here may be more useful for the detection of large bowel cancer than that in serum.     

Serum sialic acid and CEA concentrations in human breast cancer.

The concentration of bound sialic acid in the sera of 56 normal subjects and 65 subjects with breast cancer was measured, in order to determine (1) whether serum sialic acid concentrations are raised in breast cancer and (2) whether the concentration of sialic acid in serum reflects tumour stage. The amount of sialic acid in serum was compared to serum carcinoembryonic antigen (CEA) values. Urinary hydroxyproline and serum alkaline phosphatase concentrations were used as indicators of bone and liver involvement. Erythrocyte sedimentation rate (ESR) was also measured. Significantly elevated serum sialic acid concentrations were found in breast cancer, and showed correlation with tumour stage. Serum sialic acid values did not correlate with CEA values. The results suggest that measurement of serum sialic acid concentrations may be of adjunctive value in assessing tumour stage.     

CEA family syndrome. Abnormal carcinoembryonic antigen (CEA) levels in asymptomatic retinoblastoma family members.

Plasma carcinoembryonic antigen (CEA) levels were studied in all available members of 17 families in which a presumed sporadic retinoblastoma had occurred. In 9 of the 17 families, close relatives of the patient had elevated CEA levels in the absence of demonstrable disease; this we have termed the "CEA family syndrome." In two families (Nos. 8 and 17) one or both parents and all of the siblings had elevated CEA levels. To our knowledge, this is the first report of abnormal CEA levels in unaffected family members of patients with nonadenocarcinoma-type malignancies. As follow-up studies of such families become available, detection of the "CEA family syndrome" may prove to be a useful means of locating individuals with inherited premalignant or malignant conditions and may provide a stimulus for additional clinical examination of asymptomatic individuals considered at risk for developing malignancies.     

Studies on circulating antibody against carcinoembryonic antigen (CEA) and CEA-like antigen in cancer patients

Characteristics of auto-antibodies for carcinoembryonic antigen (CEA) detected in sera from 3 cancer patients (2 colorectal and 1 breast cancer) were examined. The antibodies belonged to polyclonal immunoglobulin G (IgG). The binding of auto-antibodies with the labeled CEA was inhibited by not only the unlabeled CEA but also NCA-2 (feces and meconium). However, no binding with NCA was observed. Among these auto-antibodies the antibody directed against blood group Lewis determinants which are known to be present in many purified CEA preparations was not found. Previously we had suggested that CEA, NCA-2 and NCA may contain immune determinant in common with alpha 1-acid glycoprotein (AG). These auto-antibodies showed significantly enhanced reactivity for the labeled CEA preparation after purification by anti-AG affinity chromatography in spite of no immunological reaction with AG. These results suggest that auto-antibodies are raised against the common antigenic determinants of both CEA and NCA-2 which do not exist in NCA. These antibodies might be directed to common amino acid sequence shared by CEA and NCA-2, though not excluding the carbohydrate moiety. We surveyed about 500,000 cancer patients but could find only 3 patients who showed a difference in the values of CEA by the indirect and direct method. Thus, the existence of this type auto-antibody to CEA in cancer patients is a rare phenomenon.     

Plasma carcinoembryonic antigen (CEA) as an indicator for radical or palliative radiotherapy in patients with rectal cancer

A study of 59 patients referred for radiotherapy because of inoperable or recurrent rectal cancers is presented in which a correlation is made between the response to radiotherapy and the pretreatment serum CEA level. Patients were treated radically or palliatively on the basis of clinical presentation and routine laboratory tests, but without regard to the plasma CEA level prior to treatment. The pretreatment CEA level was assessed retrospectively as an indicator of the response to treatment. Patients with a plasma CEA level in excess of 75 ng/ml had a poor prognosis, even after radical radiotherapy, whereas patients with plasma CEA less than 75 ng/ml responded better to treatment. These results suggest that plasma CEA is of value, indicating the need for radical or palliative radiotherapy. In patients with high plasma CEA at referral, radical radiotherapy appears to confer little benefit. Those with a low plasma CEA appear to respond better to radical radiotherapy, and this should be the preferred treatment in this group unless the clinical presentation indicates otherwise.     

Serum neuron-specific enolase (NSE) in patients with small cell lung cancer--comparison with carcinoembryonic antigen (CEA)

Serum neuron-specific enolase (NSE) was determined by RIA in 102 lung cancer patients. Serum NSE was elevated (greater than 10 ng/ml) in 72% (21 of 29 cases) of small cell lung cancer (SCLC) patients, which was a significantly higher positive rate than those in normal adult controls (0%, 0/48), noncancerous lung disease (17%, 4/24), squamous cell carcinoma (19%, 6/31) and adenocarcinoma (16%, 4/25) (p less than 0.05, respectively). There were no NSE-positive cases in stage I-II lung cancer patients. In SCLC, cases of extensive disease had a significantly higher NSE-positive rate (100%, 8/8) than those of limited disease (62%, 13/21) (p less than 0.05), suggesting that NSE levels were related to the bulk of the tumor. There was an excellent correlation between serum NSE and clinical response. Raised NSE levels were identified significantly more frequently than those of CEA in SCLC before chemotherapy and on relapse (or progression) (p less than 0.025, p less than 0.005, respectively). Thus, serum NSE determinations may be more useful than those of CEA for the staging and monitoring of SCLC.     

Evaluation of plasma carcinoembryonic antigen (CEA) in patients with head and neck cancer: correlation with tissue CEA staining

Forty-five patients with head and neck cancer were the subjects of the study. In most cases, plasma CEA was low and could not provide a significant clinical monitor. Two patients with poorly differentiated epidermoid carcinoma had low plasma CEA levels at the pretreatment stage, but after treatment, the levels tended to be higher because of distant metastasis. Tow other cases exhibiting undifferentiated carcinoma of the maxillary sinus at the pretreatment stage had abnormally high plasma CEA levels of 160 ng/ml and 46 ng/ml. These two patients proved the value of the correlation with cancer therapy and recurrence.     

SERUM LIPID-BOUND SIALIC ACID IN LUNG CANCER PATIENTS

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癌胚抗原半衰期在术前癌胚抗原升高的结直肠癌患者中判断预后的作用

背景与目的:癌胚抗原(carcinoembryonic antigen,CEA)监测在指导恶性肿瘤特别是结直肠癌的治疗中起重要作用。CEA半衰期作为一个较新的指标,也被应用于恶性肿瘤的监测。本研究通过检测结直肠患者术前和术后短期内的CEA水平,并计算CEA半衰期,以判断将它作为预后因素的可能性。方法:回顾性选取98例术前CEA水平升高(≥5μg/L)并有常规的术后早期CEA监测的结直肠癌根治术后患者作为研究对象。计算术后CEA半衰期,并分析它与预后的关系。结果:98例患者中,21例发生复发或远处转移,77例无复发转移。复发组术前CEA中位值(23.9μg/L)显著高于未复发组(12.3μg/L)(P=0.010);复发组术后CEA半衰期中位值为6.2天,显著长于未复发组(4.7天)(P=0.042);疾病分期越晚,预后越差(P<0.001)。术后CEA半衰期较短的患者与半衰期较长的患者相比,3年无病生存率(87%vs.66%,P=0.017)和3年总生存率(90%vs.80%,P=0.032)都较高;TNM分期较早的患者无病生存率和总生存率均较高,Ⅰ、Ⅱ、Ⅲ期患者的3年无病生存率分别为100%、93%和55%(P<0.001),3年总生存率分别为100%、98%和77%(P=0.192)。Cox回归分析表明,TNM分期和术后CEA半衰期是术前CEA水平升高的结直肠癌患者的独立预后因素。结论:除TNM分期外,CEA半衰期也可作为术前CEA水平升高的结直肠癌患者的独立预后因素。根治术后CEA半衰期延长的患者预后较差。     

Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab‐based treatment response in metastatic colorectal cancer

Carcinoembryonic antigen (CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor angiogenesis. This study aimed to evaluate baseline CEA serum levels to predict bevacizumab‐based therapy effect and survival in patients with metastatic colorectal cancer (mCRC). Two hundred and ninety eight mCRC patients receiving chemotherapy plus either bevacizumab or cetuximab were analyzed in a retrospective study. Disease control (DC), progression‐free survival (PFS), and overall survival were assessed and related to pretreatment CEA serum levels. Patients with baseline CEA serum levels below the statistical median of 26.8 ng/mL (group I) were compared with patients with higher CEA levels (group II). The cetuximab‐based treatment cohort was analyzed for specificity assessment of CEA to predict the anti‐vascular endothelial growth factor effect in mCRC. Baseline CEA serum levels inversely correlated with therapeutic response in patients receiving bevacizumab‐based treatment (disease control rate, 84% vs 60%), inversely correlated with median PFS leading to a median PFS benefit of 2.1 months for patients in group I when compared with group II, as well as inversely correlated with median overall survival (37.5 months vs 21.4 months). In an independent cohort of 129 patients treated with cetuximab‐based therapy, no association of therapeutic response or PFS with CEA serum levels was found. As expected, baseline CEA levels were prognostic for mCRC. These data give first evidence that baseline serum CEA levels might constitute an important predictor for the efficacy of first‐line bevacizumab‐based therapy in patients with mCRC.     

Immunocytochemical localization of carcinoembryonic antigen (CEA) and transport of CEA into the blood vessels in gastric cancer

CEA was localized in the luminal border, cytoplasm, but not in mucus, in Signet ring cell carcinoma (sig) and mucinous carcinoma (muc). Electronmicroscopically, CEA was localized in the glycocalyx of the microvilli and microvesicles of the cytoplasm. The histologically different cancer types showed no difference in the localization of T-CEA. We also studied P-CEA elevating factors in 38 CEA-positive (++) patients manifesting subserosal (ss) or deeper invasion. No remarkable findings were obtained. When P-CEA elevating factors were studied in 20 patients with (+) CEA reaction and ss or deeper invasion, we found that the incidence of por was high in P-CEA negative cases. In particular, the por incidence was significantly low (p less than 0.01) in patients with scirrhous type. High P-CEA levels were detected in blood adjacent to the cancer. Among 6 cases with negative P-CEA in the vessels adjacent to the cancer whose T-CEA reactions were (++) or (+), and who manifested ss or deeper invasion, there was a high incidence of por (5 cases) and scirrhous type (4 cases), histologically.     

Assessment of serial carcinoembryonic antigen (CEA) assays in postoperative detection of recurrent colorectal cancer.

Monthly serial postoperative CEA determinations, three-monthly system review plus physical examination, and a battery of six-monthly laboratory and radiologic tests were compared in order to evaluate each in detection of recurrent colorectal cancer. Twelve of the 33 patients studied prospectively developed recurrent disease. In this study CEA was found not to be a substitute for careful clinical follow-up, but if used in a serial manner it was a useful adjunct for detection of early recurrent cancer, especially intra-hepatic and retroperitoneal disease recurring in patients with elevated pretreatment CEA levels. The other laboratory and radiologic tests employed were often useful to confirm progressing disease, but they did not reveal any first evidence of recurrent disease.     

Evaluation of the measurement of serum carcinoembryonic antigen (CEA) levels using monoclonal antibody

We measured serum carcinoembryonic antigen (CEA) levels in 164 cancer patients, 153 patients with benign diseases and 45 healthy controls using monoclonal antibody and compared CEA levels by monoclonal antibody (m-CEA) with those by polyclonal antibody (p-CEA). There was a good correlation between m-CEA and p-CEA, especially in cancer patients. The positively of m-CEA was almost the same as that of p-CEA in cancer patients. But, false-positive cases by m-CEA were less common than by p-CEA in non-cancerous patients. Thus, the measurement of m-CEA was not less useful than that of p-CEA.     

Clinical use of carcinoembryonic antigen (CEA) determination]

The carcinoembryonic antigen (CEA) is a tumor marker defined by specific heterologous antisera. Elevated levels of circulating CEA have been detected by radioimmunoassay in 20-90 per cent of cases of colorectal carcinomas depending on the degree of tumor spread. The fact that elevation of CEA level can also be observed in other types of carcinomas and in several non malignant conditions greatly limit the value of the CEA test for the early diagnosis of colorectal carcinoma. Thus, the CEA assay should not be used as a screening test for cancer. Repeated CEA measurements, however, appear to be of importance for the evaluation of tumor resection and the detection of tumor recurrence. The only localized tumors known to produce elevation of CEA above the levels observed in non malignant diseases are carcinomas of the large bowel and the pancreas. In carcinomas derived from other organs a marked increase of CEA level is always associated with the presence of distant metastasis. Therefore at the present time the clinical applications of the CEA radioimmunoassay should be limited to the differential diagnosis of patients with suspicion of primary colorectal or pancreatic carcinoma, to the detection of distant metastasis in other types of carcinomas and to the post operative follow up of patients who had elevated levels of CEA before surgery. Well-controlled studies are still needed to determine if therapeutic decisions based on CEA results can lead to improved survival.     

Comparison of CA 19-9 and carcinoembryonic antigen (CEA) levels in the serum of patients with colorectal diseases

The serum levels of CA 19-9 and carcinoembryonic antigen (CEA) were determined in 37 patients with benign colorectal diseases and in 111 patients with newly discovered colorectal carcinomas or clinically verified relapses. In cancer patients, the CA 19-9 level ranged from normal (0-37 U ml-1) to 77,500 U ml-1 whereas all samples but one from patients with benign colorectal diseases had a normal value. CA 19-9 was increased in 46% and 45% of patients with an advanced (Dukes C or D) carcinoma or a verified recidive, respectively. Only one out of 26 patients (4%) with a localized (Dukes A or B) carcinoma displayed an elevated CA 19-9 level (greater than 37 U ml-1). No clear correlation was found between the CA 19-9 and CEA levels. The sensitivity of the CA 19-9 test (36%) was poorer than that of the CEA assay (69%), but the new test was markedly more specific (97% vs 70%) than the CEA assay.     

Axillary versus peripheral blood levels of sialic acid,ferritin, and CEA in patients with breast cancer

Summary Serum levels of total sialic acid, carcinoembryonic antigen (CEA), ferritin, lactate dehydrogenase, and creatine phosphokinase were measured both in tumor drainage blood (axillary vein) and in peripheral blood obtained from 121 breast cancer patients during surgery. No significant differences between mean values in peripheral and tumor draining blood, between cancer patients and healthy controls, or between patients with or without axillary lymph node metastases were found for any of the markers. Both ferritin and CEA levels were higher in axillary and peripheral blood from patients with central breast cancer versus other sites but the difference was significant only for CEA (p < 0.05). CEA levels were significantly higher (p < 0.01) in patients with > 2 cm diameter carcinomas versus T1 stage patients in axillary but not in peripheral blood. When the cephalic vein was clamped before the axillary sample was taken, ferritin showed a significant increase (p < 0.05). We conclude that measurement of sialic acid, CEA, and ferritin in axillary venous blood in breast cancer patients is not of clinical benefit, although further data are needed to clarify whether other advantages can be derived.