Tissue polypeptide antigen-specific (tps) and carcinoembryonic antigen (cea) levels in cancerous and precancerous lesions in human colon

Serum levels of tissue polypeptide antigen specific (TPS), a cytokeratin 18 marker, were determined and compared with serum levels of carcinoembryonic antigen (CEA) in 45 patients with colon adenocarcinoma and in 34 patients with benign diseases (adenomatous polyps and ulcerative colitis) at the time of diagnosis. In colon carcinoma patients 58% had an elevated TPS level (cut-off 100 U/l) and 53% had an elevated CEA level (cut-off 3.0 ng/ml). The sensitivity of the cytokeratin marker TPS was related to the stage of the disease. Significant correlation was observed between TPS and Dukes stages in colon cancer patients and the highest TPS values were achieved in Dukes stage D. The combined use of the two markers increased the sensitivity to 82% compared with the use of only one. Simultaneous raise of both serum markers TPS and CEA was observed in 36% of cases. In the majority of the patients with adenomatous polyps and ulcerative colitis the serum TPS and CEA levels were below the upper reference limit. However the initial high levels in some patients could be considered as a prognostic indicator for identifying a group of patients with increased risk of cancer development. No significant correlation was observed between serum TPS and CEA concentrations in individual patients with benign diseases.     

DNA aneuploidy in colorectal adenomas

The frequency of DNA aneuploidy was investigated by flow cytometry in 156 colorectal adenomas including 56 associated with 36 synchronous adenocarcinomas. Nine of 156 adenomas (6%) were DNA aneuploid. DNA aneuploidy correlated with increasing size (P less than 0.005) and histopathological type P less than 0.05) but not with dysplasia. Adenomas in associated with a synchronous adenocarcinoma did not have an increased incidence of DNA aneuploidy. Adenocarcinomas found in association with adenomas tend to have a lower incidence of DNA aneuploidy then the generality of colorectal cancers.     

ras蛋白在食管癌及食管癌前病变组织中的表达

目的了解中国食管癌高发区食管癌变发生过程中癌基因ｒａｓ的变化。方法采用卵白素－生物素－辣根过氧化氢酶复合物（ＡＢＣ）方法测定食管癌高发区食管癌及癌前病变组织中癌基因ｒａｓ蛋白的表达状况。结果在正常食管上皮和癌前病变组织中未见ｒａｓ蛋白表达,而３６例食管癌组织有９例出现免疫阳性反应,其免疫阳性反应率为２５％。结论ｒａｓ癌基因表达是食管癌变晚期阶段的一个分子学变化。     

Nucleolar organizer regions in precancerous and cancerous lesions of the bronchus

Using a silver staining technique, nucleolar organizer region-associated proteins (Ag-NOR) were studied in paraffin sections of five specimens of normal bronchial epithelium, eight of atypical squamous metaplasia, five of carcinoma in situ, and seven of microinvasive squamous cell carcinoma. The mean number of Ag-NOR in the nucleus were normal epithelium 1.2 +/- 0.1 (mean +/- SD), atypical squamous metaplasia (borderline lesion) 2.2 +/- 0.5, carcinoma in situ 3.8 +/- 0.6, and microinvasive squamous cell carcinoma 4.8 +/- 1.1. There was a highly significant difference between the Ag-NOR numbers in the atypical squamous metaplasia and those in the carcinoma in situ (P less than 0.01). The Ag-NOR staining is a useful technique for the differential diagnosis of difficult borderline lesions in the bronchial epithelium.     

肺癌及癌前病变组织芯片中PTEN的表达及其意义

目的检测肺癌组织中PTEN蛋白的表达,并探讨其在肺癌发生、发展中的作用和意义。方法利用组织芯片技术和免疫组化方法,检测原发性肺癌89例、淋巴结转移性肺癌12例、癌前病变12例和正常肺标本10例中PTEN蛋白的表达情况。结果原发性肺癌中PTEN阳性率为44.9%,显著低于正常组(90.0%)(P<0.05);PTEN的表达与分化程度、淋巴结转移和临床分期相关(P<0.05)。结论PTEN蛋白在肺癌中的表达阳性率降低,并且与病情进展程度相关,PTEN的失活促进了肿瘤的发生和发展,与预后不良相关。     

Expression of cyclooxygenase-2 and DNA topoisomerase II alpha in precancerous and cancerous lesions of the oral mucosa

The involvement of cyclooxygenase (COX)-2 in oral carcinogenesis and outcome of the patients is not fully understood. To determine whether COX-2 expression could serve as an indicator for them, we examined the expression of COX-2 and DNA topoisomerase (DNA-Topo) II alpha as an index of cell proliferating activity in precancerous and cancerous lesions of the oral mucosa. A 164 samples composed of 60 intraepithelial dysplasias (IEDs), 12 carcinomas in situ (CISs), 72 squamous cell carcinomas (SCCs) including 12 early invasive SCCs, 10 undifferentiated carcinomas (UCs), and 10 epithelial hyperplasias (EHPs) in the oral mucosa were examined immunohistochemically for COX-2 and DNA-Topo II alpha. Normal squamous epithelium as the control showed no COX-2 expression, whereas 41% of IEDs, 67% of CISs, 74% of SCCs, and 86% of UCs demonstrated increased COX-2 expression with elevated DNA-Topo II alpha labeling index (LI). High COX-2 expression was also observed in 61% of EHPs, but DNA-Topo II alpha LI was very low. Increased expression of COX-2 protein correlated with elevated DNA-Topo II alpha LI, indicating that COX-2 may contribute to malignant transformation and tumor growth. These two enzyme activities were increased as T, N, and M categories and stages proceeded. The patients with high expression of both COX-2 and DNA-Topo II alpha showed poor prognosis. Our results suggested that COX-2 expression become a possible indicator in oral carcinogenesis and may reflect the outcome of the patients.     

结直肠癌前病变及肿瘤患者血清代谢物的差异分析

目的:应用核磁共振方法检测结直肠肿瘤患者及结直肠癌前病变患者血清代谢物质水平变化.方法:收集新疆医科大学第一附属医院确诊结直肠癌患者血清标本40例,新疆医科大学第一附属医院考虑为癌前病变(包括溃疡性肠病、结直肠腺瘤)患者血清标本20例,健康对照组血清标本60例,应用核磁共振技术结合偏最小二乘法,分析三组中血清代谢物质的变化水平.结果:结直肠肿瘤患者血清中的苯丙氨酸、酪氨酸、乳酸、β-葡萄糖、胆碱、亮氨酸、甘氨酸、α-葡萄糖、肌酸、谷氨酰胺、谷氨酸、乙酰半胱氨酸、缬氨酸、脯氨酸丙氨酸等14种化合物较正常者明显下降,而β-羟丁酸、乙酰乙酸的含量升高,差异有统计学意义(P<0.05).结直肠癌前病变患者与肿瘤患者血清亮氨酸、胆碱、β-葡萄糖均比健康者低.除了上述三种化合物以外,结直肠癌前病变患者血清异丁酸、甜菜碱、柠檬酸较健康组低(有统计学差异).结论:以代谢组学为基础的核磁共振技术在结直肠肿瘤的早期诊断中有无创、快速、灵敏度高等临床应用价值.结直肠肿瘤患者与健康者比较,部分血清代谢物质有变化.结直肠癌前病变组患者血清代谢物质的变化呈从正常至肿瘤的过渡变化状态,其部分相关代谢物质的变化间接的预示肿瘤的发生.     

Tissue carcinoembryonic antigen and estrogen receptor in human breast cancer

Sixty-six human ductal infiltrative breast carcinomas were examined for their estrogen receptor (ER) by the dextran-coated charcoal procedure and for the presence of carcinoembryonic antigen (CEA) by immunofluorescence with the aid of monoclonal antibodies. Statistically significant differences in CEA positivity were found between stage III (33%) and stage II (19%) tumors (Z = 2.08; p less than 0.02) and between ER + (22%) and ER- (37%) tumors (Z = 2.083; p less than 0.02). An inverse correlation was observed between positivity and receptor concentrations. No difference in CEA positivity was observed between pre- and post-menopausal women.     

Safety and immunogenicity of a DNA vaccine encoding carcinoembryonic antigen and hepatitis B surface antigen in colorectal carcinoma patients.

Despite an abundance of preclinical data, relatively little is known regarding the efficacy of DNA vaccination in humans. Here, we present results from a dose-escalation clinical trial of a dual expression plasmid encoding carcinoembryonic antigen (CEA) and hepatitis B surface antigen (HBsAg) in 17 patients with metastatic colorectal carcinoma. CEA was selected as a prototypic tumor-associated self-antigen, and the HBsAg cDNA was included as a positive control for immune response to the DNA vaccine without relying upon breaking tolerance to a self-antigen. Groups of 3 patients received escalating single i.m. doses of the DNA vaccine at 0.1, 0.3, and 1.0 mg. Subsequent groups of 3 patients received three repetitive 0.3- or 1.0-mg doses at 3-week intervals. A final group of 2 patients received three repetitive 2.0 mg doses at 3-week intervals. Toxicity was limited to transient grade 1 injection site tenderness, fatigue, and creatine kinase elevations, each affecting a minority of patients in a non-dose-related manner. Repetitive dosing of the DNA vaccine induced HBsAg antibodies in 6 of 8 patients, with protective antibody levels achieved in four of these patients. CEA-specific antibody responses were not observed, but 4 of 17 patients developed lymphoproliferative responses to CEA after vaccination. No objective clinical responses to the DNA vaccine were observed among this population of patients with widely metastatic colorectal carcinoma. Nevertheless, this pilot trial has provided encouraging human immune response data in support of this vaccine technology.     

Heteromorphisms of C-bands in patients with precancerous and cancerous lesions of the cervix uteri

C-band heteromorphisms of chromosomes 1, 9 and 16 were studied in 62 patients with cervical cancer, 100 women with various grades of precancerous lesions and 47 normal women as controls. The data showed an increased frequency of heteromorphisms of chromosome 1 in patients with cancer (48.39%) and severe dysplasias (40%) as compared to controls (29.8%) and lower grades of dysplastic lesions, i.e. mild and moderate (28.8%). The increase in the incidence of chromosome 1 heteromorphisms in cancer was found to be statistically significant (p less than 0.05) compared to controls. The present study indicates that C-band heteromorphisms may play some role in the development of malignancy of the uterine cervix.     

Tissue polypeptide-specific antigen and carcinoembryonic antigen for early prediction of recurrence in lung adenocarcinoma

Fifty patients with lung adenocarcinoma, including 20 cases with recurrence and 30 cases without recurrence 1 year after operation, were enrolled in this study. The serial serum levels of tissue polypeptide-specific antigen (TPS) and carcinoembryonic antigen (CEA) were measured before operation and at 1 week, and at 1, 3, 6, 9, and 12 months after operation for early detection of recurrence. The results revealed that: 1) mean serum values of TPS were significantly higher at 1, 3, 6, 9, and 12 months after operation in 20 patients with recurrent adenocarcinoma, when compared with 30 patients without recurrent adenocarcinoma; 2) mean serum values of CEA were significantly higher at 9 months and 12 months after operation in 20 patients with recurrent adenocarcinoma, when compared with 30 patients without recurrent adenocarcinoma. We conclude that TPS is a better marker than CEA for early prediction of adenocarcinoma recurrence in lung within 1 year after operation. However, a longer follow-up study should be encouraged.     

Leukocyte alkaline phosphatase and carcinoembryonic antigen in metastatic colorectal cancer patients

Peripheral blood leukocyte alkaline phosphatase scores and plasma carcinoembryonic antigen levels in 26 patients with metastatic colorectal cancer were compared to those in 30 healthy controls. Patients had metastases to the liver and abdomen. The mean leukocyte alkaline phosphatase score in the metastatic colorectal cancer patients was significantly higher than in the control group (246 +/- 65 vs, 52 +/- 26, p less than 0.001); and the mean carcinoembryonic antigen level in the patients was also significantly higher than in the controls (110 +/- 100 vs, 4.9 +/- 3 ng/ml, p less than 0.001). One hundred percent of the metastatic cancer patients had elevated LAP scores and 73% of these patients had elevated CEA levels. There was a difference between the mean CEA levels in the patients with liver metastases and those with abdominal metastases (162 +/- 135 vs, 39 +/- 53 ng/ml, p less than 0.04). The results suggest that although both markers were elevated in metastatic colorectal cancer, the LAP score seems to be more useful in detecting metastatic disease, since we found 11% false negatives with the CEA level and 0% false negatives with the LAP score.     

Chemotherapy-induced carcinoembryonic antigen surge in patients with metastatic colorectal cancer

OBJECTIVES: To investigate the incidence of carcinoembryonic antigen (CEA) surge in patients with metastatic colorectal cancer (MCRC) and its implications on clinical outcome. METHODS: A retrospective chart review of patients with MCRC treated with chemotherapy at Roswell Park Cancer Institute from January 2000 to May 2004 was conducted. A CEA surge was defined as an increase of >20% from baseline followed by a >20% drop in one or more subsequent CEA levels compared to baseline. The incidence of CEA surge and its association with clinical outcome was investigated. RESULTS: Eighty-nine patients were evaluable for CEA surge. A CEA surge was documented in 10 patients. The CEA surge lasted <4 months in all 10 patients and was associated with a clinical benefit. No significant correlation was noted between CEA surge and site of primary tumor, site of metastatic disease, or tumor differentiation. CONCLUSIONS: CEA surges can be observed in patients receiving chemotherapy for MCRC and are often associated with a clinical benefit. None of the CEA surges satisfied the American Society of Clinical Oncology definition of CEA progression. A rise in CEA after initiation of chemotherapy, unless lasting >4 months, cannot be used as an indicator of progressive disease.     

Specific adhesion of carcinoembryonic antigen-bearing colorectal cancer cells to immobilized carcinoembryonic antigen.

Recent characterization of the genomic structure of carcinoembryonic antigen (CEA) is consistent with that of a cellular adhesion molecule. To examine this function in colorectal cancer, the adherence of cell lines to microtiter wells coated with CEA and well-described adhesive molecules was determined. The CEA-positive cell line LoVo and the CEA-devoid cell line H-Meso-1 did not differ in adherence to the extracellular matrix proteins laminin, collagen and fibronectin, whereas LoVo cells adhered to CEA (10 micrograms/well) in a specific manner (43% bound cells vs. 1.5% bound cells with BSA or alpha-acidglycoprotein controls, P less than 0.01) while H-MESO-1 showed no adhesion to CEA (less than 0.6% bound cells). This adhesion of LoVo cells to CEA was not affected by co-incubation of cells with EDTA, sodium azide, or at 23 degrees C. However, the CEA to CEA adhesive interaction was inhibited by a monoclonal antibody directed against an epitope in the N-terminal domain of the CEA molecule, and decreased by enzymatic removal of CEA from the LoVo cell membrane. The extent of adhesion to immobilized CEA by four CEA-producing cell lines (LoVo, HT29, LS174T and LS174-S), correlated with membrane CEA expression as determined by FACS analysis. The results of these experiments add support to the concept that CEA may function as a specific homotypic cellular adhesion molecule for colorectal cancer cells.     

The prognostic value of serum carcinoembryonic antigen in colorectal carcinoma

Background. Carcinoembryonic antigen (CEA) is a non-specific tumor marker, however some clinical applications have been reported. Aims. Our aim is to define the role of pretherapeutic serum CEA level (SCEAL) as prognostic factor and to describe the usefulness of serial SCEAL in the follow-up of Mexican patients with completely resected colorectal carcinoma (CRC). Patients and methods. A retrospective cohort study of 580 patients with CRC treated in Mexico City in a 12-year period. The Cox’s model was used to evaluate prognostic factors predicting survival and the logistic regression model was used to test recurrence determinants in completely resected CRC. Sensitivity and specificity for SCEAL as diagnostic aid of recurrence after complete resection is reported and receiver-operating characteristic curve (ROC) analysis was performed to choose the best cutoff point. Results. Histologic grade, Dukes’ stage, curative resection and age were independent factors determining survival. Preoperative SCEAL was not found to be significant, however a bivariate correlation between preoperative SCEAL and Dukes’ stage was found. Dukes’ stage and specially lymph node metastasis were significant recurrence determinants in completely resected CRC. The sensitivity and specificity of serial SCEAL as diagnostic aid for recurrence after complete resection was 58% and 91%, respectively, using 10 ng/ml as cutoff point. Conclusions. Preoperative SCEAL is neither a significant prognostic factor nor a significant determinant of recurrence. Serial SCEAL has a limited role in the follow-up of patients with completely resected CRC. However, the high specificity for diagnosis of recurrences supports its use in CEA-based second-look surgery.