Tissue Carcinoembryonic Antigen Research Articles

Carcinoembryonic antigen (CEA) expression in human tumors: A tissue microarray study on 15,413 tumors.

e15181 Background: Carcinoembryonic antigen (CEA) is a cell surface glycoprotein which is overexpressed in various cancers but reported prevalence data vary considerably for many tumor types. Because of its overexpression in various cancer types and the limited expression in normal tissue CEA has become a potential drug target with several potential drug candidates currently being evaluated. CEA is also shed into the blood stream, so that CEA measurement in the serum is used as a tool for early detection and recurrence monitoring of cancer. Methods: To comprehensively determine CEA expression in normal and neoplastic tissues, a tissue microarray containing 15,413 samples from 120 different tumor types and subtypes as well as 76 different normal tissue types were analyzed by immunohistochemistry. Results: CEA was detectable in 65 (54.2%) of 120 tumor categories including 49 (40.8%) tumor types with at least one strongly positive case. CEA positivity was most common in colorectal adenomas (100%) and carcinomas (98.7%), other gastrointestinal adenocarcinomas (61.1%-80.3%), medullary carcinomas of the thyroid (96.3%), pulmonary adenocarcinoma (73.7%), mucinous carcinomas of the ovary (79.8%) and the breast (43.2%), squamous cell carcinomas of various sites (30.2%-69.1%), and small cell carcinomas of the lung (64.3%), the urinary bladder (38.9%), and the prostate (50.0%) as well as non-invasive papillary urothelial carcinoma pTa G3 (33,6%), pTa G2 high-grade (25,0%) and pTa G2 low-grade (5,7%). High CEA expression was linked to high grade tumors (p < 0.0001) and invasive growth (p < 0.0001) in urinary bladder cancer as well as estrogen receptor positivity (p = 0.0005) and HER2 positivity (p = 0,0158) in invasive breast cancer of no special type. In 1.250 colorectal adenocarcinomas, reduced CEA expression was associated with mismatch repair deficiency (p < 0.0001) but not with pT and pN stage. CEA expression level was unrelated to clinico-pathological tumor parameters in adenocarcinomas of the pancreas and the stomach, endometroid endometrium carcinoma as well as in serous and endometroid carcinomas of the ovaries. Conclusions: In summary, CEA is abundantly expressed in a broad range of epithelial neoplasms. Our data thus identify various tumor entities where CEA positive cancers might best benefit from CEA serum monitoring and anti-CEA therapies.

Clinical implication of tissue carcinoembryonic antigen expression in association with serum carcinoembryonic antigen in colorectal cancer

This study aimed to evaluate the prognostic significance of carcinoembryonic antigen (CEA) expression in tumor tissues of patients with colorectal cancer (CRC). The cohort included 7,412 patients with CRC from January 2010 to December 2015. Survival outcomes were assessed based on tissue CEA (t-CEA) patterns and intensities. Three-year (76.7% versus 81.3%) and 5-year (71.7% versus 77.6%, p < 0.001) disease-free survival (DFS) rates were significantly (p < 0.001) poorer in patients with a diffuse-cytoplasmic pattern than an apicoluminal pattern. Three-year (79% versus 86.6%) and 5-year (74.6% versus 84.7%) DFS rates were also significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Three-year (84.6% versus 88.4%) and 5-year (77.3% versus 82.6%) overall survival (OS) rates were significantly (p < 0.001) poorer in patients with diffuse-cytoplasmic than apicoluminal pattern of CEA expression, and both 3-year (86.7% versus 91.2%) and 5-year (80.1% versus 87.7%) OS rates were significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Multivariate analyses showed that high-intensity t-CEA was independently associated with DFS (p = 0.02; hazard ratio [HR] = 1.233) and OS (p = 0.032; HR = 1.228). Therefore, high-intensity t-CEA is a significant prognostic factor in CRC, independent of serum CEA (s-CEA), and can complement s-CEA in predicting survival outcomes after CRC resection.

NIR fluorochrome labeled anti-carcinoembryonic antigen monoclonal antibody for gastric cancer-specific image guided surgery.

340 Background: Carcinoembryonic antigen (CEA) is a widely known tumor marker that is clearly expressed in gastrointestinal tract cancer. We utilized a CEA-specific chimeric antibody conjugated to a near infrared (NIR) fluorophore to facilitate CEA-targeted fluorescence image–guided surgery (FGS) of gastric cancer. The anti-CEA antibody, SGM-101 is conjugated with NIR dye BM-105, which has an absorbance band centered at 705 nm. Methods: RNA sequencing data of 34 gastric cancer cell lines from Cancer Cell Line Encyclopedia were screened and validated by qPCR and western blotting. Flow cytometry and confocal microscopy were performed by SGM-101, Alexa Fluor-680, Isotype-101 and Isotype-680 to quantify fluorescence intensity. SGM-101(n = 5) or Isotype-101(n = 2) was injected to mouse xenografts through a tail vein which had been subcutaneously implanted with MKN-45, SNU-16, and SNU-668. IVIS Spectrum quantified radiant efficiency of fluorescence in the region of interest at serial time points. The extracted tumor in peak time was analyzed by confocal imaging for microdistribution. In addition, 85As2mLuc were injected intraperitoneally in 6-week-old female BALB/c-nu mice for peritoneal carcinomatosis. Bioluminescence/fluorescence imaging was performed with IVIS Spectrum at peak time and analyzed via Living Image. Histologic evaluations were processed with H&amp;E and Immunohistochemistry (IHC) data by a pathologist. Results: RNA expression of ceacam5 and protein expression of CEA in gastric cell lines was measured by RNA sequencing, qPCR, and western blotting. CEA expression patterns displays similar with fluorescence intensity patterns which were quantified through flow cytometry and immunocytochemistry show that CEA localized in membranes. In subcutaneously implanted model, the radiant efficiency of each group shows that the accumulation of SGM-101 has significantly higher fluorescence signal in the high CEA expressing group (MKN-45) and medium expressing group (SNU-16) while no fluorescence signal was observed in the CEA negative group (SNU-668) via IVIS Spectrum. Biodistribution of SGM-101 indicates that the maximum peak accumulation point was 48 hours after tail vein injection. Frozen tissue which was extracted at peak detection time shows micro-distribution of SGM-101 and expression of extracted tissue CEA expression was validated with IHC by pathological analysis. In the peritoneal carcinomatosis model, the imaging of fluorescence detection patterns corresponds with bioluminescence imaging and histological evaluation. Conclusions: CEA expression corresponded with intensity of in vitro fluorescence immunodetection and a tumor area accumulation in gastric cancer xenografts by SGM-101. This study indicates that NIR tumor specific imaging can be a feasible tool for image-guided surgery.

Study of Fe₃O₄-PPy Core-Shell Nanocomposite in the Diagnosis of Tumor Markers in the Tissues of Early Gastric Cancer Patients.

In order to study Fe₃O₄-Polypyrrole (Fe₃O₄-PPy) core-shell nanocomposite in the diagnosis of tumor markers in the diseased gastric tissues of early cancer patients, a total of 160 cases of patients, who were confirmed as early gastric cancer by gastroscopy or postoperative pathology at a designated hospital of the study from December 2014 to December 2018, were selected as research objects and were divided into two groups of observation and control group with 80 cases in each group. For each patient in the two groups, two pieces of diseased gastric tissue were firstly taken through gastroscopy; then the observation group applied Fe₃O₄-PPy with the particle diameter of 150-350 nm as carrier to detect the contents of carbohydrate antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), carbohydrate antigen 242 (CA242), carcinoembryonic antigen (CEA) and carbohydrate antigen 72-4 (CA72-4) in the diseased gastric tissue, while the control group directly detected the contents of corresponding tumor markers; after the detections, the sensitivity, specificity and diagnostic efficiency of each marker in the two groups of patients were calculated, and receiver operating characteristics (ROC) curves with the areas under the curves (AUC) were drawn to analyze the correlation between the level of Fe₃O₄-PPy and the detection efficiency of gastric cancer markers. The results show that the detection sensitivity (82.17%, 80.32%, 79.48%, 84.63%, and 85.66%) and specificity (76.75%, 79.66%, 81.07%, 83.47%, and 85.24%) of CA19-9, AFP, CA242, CEA, and CA72-4 in the tumor tissue of patients in observation group for the diagnosis of early gastric cancer are higherthan the sensitivity (78.66%, 79.25%, 76.18%, 82.11%, and 83.45%) and specificity (74.37%, 76.94%, 77.24%, 81.22%, and 81.59%) of that in control group with statistically significant differences (P < 0.05). Therefore, it is believed that the Fe₃O₄-PPy is of great significance for the detection of early gastric tumor markers in the tissues of patients with early gastric cancer, and has certain value for the auxiliary diagnosis of early gastric cancer and the observation of therapeutic effects. This study results provide a reference for the further researches of Fe₃O₄-PPy in the diagnosis of tumor markers in patients with early gastric cancer.

Clinical significance and expression of circular RNA circ_0076704 in human gastric carcinoma

Objective To investigate the clinical significance of circular RNA circ_0076704 RNA in human gastric carcinoma. Methods Human gastric cancer and matched normal gastric tissue were collected, and circ_0076704 were detected by fluorescence quantitative real-time polymerase chain reaction assay. The relation of between circ_0076704 expression and patient’s sex, age, tumor location, tumor diameter, histological differentiation, depth of tumor invasion, lymph node metastasis, distant metastasis, TNM staging and carcinoembryonic antigen (CEA) levelv and helicobacter pylori (HP) infection and other clinicopathological factors was analyzed, respectively. Results The expression of circ_0076704 was not significantly correlated with patient sex (χ2=1.269, P=0.260), age (χ2=0.139, P=0.709), tumor location (χ2=0.543, P=0.709), tumor diameter (χ2=2.222, P=0.136), degree of tissue differentiation (χ2=4.484, P=0.106), CEA level (χ2=0.135, P=0.714) and HP infection (χ2=0.834, P=0.361), but with the depth of tumor invasion (χ2=11.349, P=0.010). Lymph node metastasis (χ2=11.929, P=0.008), distant metastasis (χ2=10.909, P=0.001), TNM stage (χ2=15.503, P=0.001) and five year survival (χ2=7.519, P=0.006) were significantly correlated. Further studies from ROC curves showed that circ_0076704 sensitivity and specificity were 0.90 and 0.85, respectively. Conclusion Circ_0076704 is highly expressed in gastric cancer tissues and could be used as a molecular marker for gene diagnosis and treatment of gastric cancer. Key words: Gastric carcinoma; Tumor maker; Circular RNA; Significance

Lectin-Based Assay for Glycoform-Specific Detection of α2,6-sialylated Transferrin and Carcinoembryonic Antigen in Tissue and Body Fluid.

Antibodies are useful for detecting glycoprotein antigens, but a conventional antibody recognizes only a protein epitope rather than a glycan. Thus, glycan isoform detection generally requires time- and labor-consuming processes such as lectin affinity column chromatography followed by sandwich ELISA. We recently found antigen-antibody reactions that were inhibited by lectin binding to glycans on the glycoprotein antigen, leading to a convenient glycoform-specific assay. Indeed, Sambucus sieboldiana agglutinin (SSA) lectin, a binder to sialylα2,6galactose residue, inhibited antibody binding to α2,6-sialylated transferrin (Tf) (SSA inhibition). SSA inhibition was not observed with other glycoforms, such as periodate-treated, sialidase-treated and sialidase/galactosidase-treated Tf, suggesting that the assay was glycoform-specific. SSA inhibition was also applicable for visualizing localization of α2,6-sialylated-Tf in a liver section. This is the first immunohistochemical demonstration of glycoform localization in a tissue section. SSA inhibition was utilized for establishing ELISA to quantify α2,6-sialylated carcinoembryonic antigen (CEA), a marker for various cancers. In addition, α2,6-sialylated-CEA was visualized in a colonic adenocarcinoma section by SSA inhibition. The method would further be applicable to a simple and rapid estimation of other α2,6-sialylated glycoproteins and have a potential aid to histopathological diagnosis.

Relations of carcinoembryonic antigen (CEA) staining of cancer tissue and serum CEA levels to histologic response in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemoradiotherapy (nCRT).

790 Background: Neoadjuvant chemoradiotherapy (nCRT) is a standard of care for LARC. The serum CEA level is a predictor of the response to nCRT; however, the relation between CEA production immunohistochemically evaluated in cancer tissue and treatment response remains unclear. Methods: The study group comprised 145 patients with clinical Stage II/III rectal cancer who received nCRT followed by surgery from 2005 through 2013. The radiation dose was 40 to 45 Gy. UFT- or S-1-based chemotherapy was given concurrently. Surgery was performed 6 to 8 weeks after the completion of radiotherapy. Immunohistological CEA staining patterns in biopsy tissue obtained before nCRT were evaluated. Specimens in which the luminal cell membrane or the cytoplasm was strongly stained were defined as staining positive. The histologic response was evaluated on the basis of the pathological complete response (ypCR) rate, T downstaging, tumor regression grade (TRG), and tumor shrinkage rate on MRI. Results: CEA staining in biopsy specimens and serum CEA levels were both negative in 17 patients (11.7%) and both positive in 72 patients (49.7%). There was no relation between the groups (p = 0.174). In patients with negative CEA staining, the rates of ypCR, T downstaging, marked regression, and mean tumor shrinkage were 24.3%, 51.4%, 45.9%, and 72.3%, respectively. In patients with positive CEA staining, these rates were 11.1%, 48.1%, 37.0%, and 72.8%, respectively. CEA staining of cancer tissue was not significantly related to the ypCR rate, T downstaging, a marked regression rate, or the tumor shrinkage rate on MRI (p = 0.060, p = 0.849, p = 0.436, and p = 0.874, respectively). Patients with negative serum CEA levels before nCRT had significantly higher rates of ypCR, T downstaging, marked regression, and tumor shrinkage on MRI than did patients with positive serum CEA levels (p = 0.014, p = 0.006, p = 0.002, and p = 0.014, respectively). Conclusions: Serum CEA levels before nCRT were a significant predictor of the histologic response to nCRT; in contrast, tissue CEA staining before nCRT was unrelated to the histologic response to nCRT.

Biochemical Evidence for the Antitumor Potential of Garcinia mangostana Linn. On Diethylnitrosamine-Induced Hepatic Carcinoma.

Background:Garcinia mangostana is extensively used in most of the Indian herbal pharmaceuticals and nutraceuticals.Objective:The objective of this study was to elucidate the underlying biochemical protective mechanism of G. Mangostana Linn. fruit extract (GME) in deterioration of diethylnitrosamine (DEN)-induced hepatic carcinoma (HCC) in rats.Materials and Methods:The cancer was induced using DEN to the experimental rats and treated with GME (200, 400, and 600 mg/kg) to find its anticancer property. The cancer biomarkers such as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), hepatic hydroxyl proline, total tissue protein, and tumor necrosis factor-alpha levels were measured using ELISA. The vascular endothelial growth factor expressions were also seen in liver tissues using immunohistochemistry.Results:In addition, there was a significant increase in serum AFP, CEA, hepatic hydroxylproline, and total tissue protein levels in HCC group versus the negative control group. In contrast, the groups with HCC subjected to either high or low dose of GME elicited significant reduction of AFP, CEA, hepatic hydroxylproline, and increase in total protein in serum compared to the untreated HCC rats. Interestingly, treatment with GME elicited marked improvement in the liver histological feature and downregulation of tumor necrosis factor-alpha levels in HCC groups. GME extract may have chemopreventive benefits by reducing the tumor promoting growth factor levels in HCC-induced group.Conclusion:To sum up, all findings on curative groups had proved clearly that the GME has anticarcinogenic effect on the development of liver cancer induced by DEN in rats.SUMMARY Garcinia mangostana Linn. (GME) may have chemopreventive property by reducing the tumor promoting growth factor and tumor necrosis factor-alpha levels in diethylnitrosamine (DEN)-induced hepatic cancerThe suppression in the levels of cancer biomarkers by GME due to the presence of anticancer phytoconstituentsThe histological studies proved the effective dose of GME against DEN-induced experimental hepatic cancer. Abbreviations used: TNF-α: Tumor necrosis factor-alpha, PBS: Phosphate buffered saline, ROS: Reactive oxygen species, DNA: Deoxyribonucleic acid, GSH: Glutathione, VEGF: Vascular endothelial growth factor.

Low expression of hsa_circ_0006633 in human gastric cancer and its clinical significances.

Circular RNAs are new type of endogenous RNAs, which play an important role in the regulation of gene expression and indicate a great capacity in clinical diagnosis and treatments of diseases. However, the role of circular RNAs in gastric cancer remains unknown. In this study, we chose hsa_circ_0006633 as the target circular RNA and measured its levels in human gastric cancer tissues, plasma, and gastric cell lines by real-time quantitative reverse transcription polymerase chain reaction. Hsa_circ_0006633 levels at multiple stages of gastric tumorigenesis were then explored, and its relationships with clinicopathological features were analyzed as well. We found that the expression levels of hsa_circ_0006633 in four gastric cancer cell lines, HGC-27, SGC-7901, MGC-803, and AGS, were downregulated than those in normal gastric mucosal epithelial cell line GES-1. Then, we further detected that it was downregulated in 79.2% (76/96) gastric cancer tissues compared with the adjacent non-tumorous tissues. The lower expression of hsa_circ_0006633 was associated with cancer distal metastasis ( p = 0.037) and tissue carcinoembryonic antigen level ( p = 0.041). In addition, hsa_circ_0006633 expression was significantly decreased in gastritis and dysplasia tissues comparing with the healthy control. Moreover, plasma hsa_circ_0006633 levels were significantly increased in gastric cancer compared with healthy control. Our data imply that hsa_circ_0006633 may play an important role in gastric carcinogenesis and is also a potential biomarker for screening gastric cancer.

Global circular RNA expression profile of human gastric cancer and its clinical significance.

Circular RNAs (circRNAs) are a new class of noncoding RNAs. However, the expression profile and clinical significance of circRNAs in human gastric cancer is unclear. The global circRNA expression profile in human gastric cancer was measured by circRNA microarray. Hsa_circ_0014717, one of the most downregulated circRNAs in microarray, was selected as a targeted circRNA to explore its levels in gastric tissues and gastric juice. Freeze‐thaw experiment and incubation experiment confirmed the stability of gastric juice circRNAs. A total of 308 circRNAs, including 107 (34.74%) upregulated and 201 (65.26%) downregulated circRNAs, were found significantly aberrantly expressed in gastric cancer tissues. The top ten upregulated in gastric cancer tissues were hsa_circ_0035445, hsa_circ_0003789, hsa_circ_0063809, hsa_circ_0074362, hsa_circ_0006282, hsa_circ_0011107, hsa_circ_0084606, hsa_circ_0005556, hsa_circ_0050547, and hsa_circ_0006470, while the top ten downregulated ones were hsa_circ_0007099, hsa_circ_0001897, hsa_circ_0007707, hsa_circ_0008832, hsa_circ_0001546, hsa_circ_0002089, hsa_circ_0004680, hsa_circ_0000154, hsa_circ_0004458, and hsa_circ_0008394. The hot‐point chromosomes were chr1, chr2, chr3, chr9, and chr17. Hsa_circ_0014717 was significantly downregulated in 77.2% (74/96) gastric cancer tissues. Its levels in gastric cancer tissues were related to tumor stage (P = 0.037), distal metastasis (P = 0.048), tissue carcinoembryonic antigen (P = 0.001), and carbohydrate antigen 19‐9 expression (P = 0.021). More importantly, hsa_circ_0014717 can stably exist in human gastric juice; and its nature meets the requirements of clinical detection. Our study uncovered the circRNA expression profile in human gastric cancer. Moreover, some circRNAs can stably exist in human body fluid, and has the potential to be used as novel biomarkers for the screening of high‐risk gastric cancer patients.

Decreased expression of hsa_circ_0001895 in human gastric cancer and its clinical significances.

Circular RNAs are a special class of endogenous RNAs characterized by jointing 3' and 5' ends together via exon or intron circularization. Recent studies found that circular RNAs are involved in the development of some human diseases. However, little is known about their roles in human gastric cancer. In this study, we chose hsa_circ_0001895 as a targeted circRNA to investigate its clinical significances in gastric cancer patients. Hsa_circ_0001895 expression levels in five gastric cancer cell lines and 257 specimens of tissues were measured by real-time quantitative reverse transcription polymerase chain reaction. Then, the potential relationship between hsa_circ_0001895 expression levels and patients' clinicopathological factors was investigated. A receiver operating characteristic curve was constructed for evaluating the diagnostic value of hsa_circ_0001895. Hsa_circ_0001895 expression levels in five detected gastric cancer cell lines (AGS, BGC-823, HGC-27, MGC-803, and SGC-7901) were all significantly downregulated than those in normal gastric epithelial GES-1 cells. Besides, compared with healthy control tissues, it was downregulated not only in 69.8% (67/96) gastric cancer tissues but also in gastric precancerous lesions. Moreover, hsa_circ_0001895 expression levels were significantly correlated with cell differentiation, Borrmann type, and tissue carcino-embryonic antigen expression. Our results suggested that hsa_circ_0001895 may play crucial roles during gastric cancerogenesis and is a potential biomarker for clinical prognosis prediction.

Expression and significance of carcinoembryonic antigen, cancer antigen 153, and cyclooxygenase-2 in breast cancer ⁎

Abstract Objective This study aimed to evaluate serum and nipple discharge levels of carcinoembryonic antigen (CEA) and cancer antigen 153 (CA153) and tissue cyclooxygenase-2 (COX-2) expression in breast cancer cases and associations of these proteins with breast cancer metastasis. Methods The immunohistochemical Ultra Sensitive TM S-P method was used to detect COX-2 expression in 77 cases of invasive breast carcinoma. Of these cases, 52 exhibited CEA and CA153 in both serum and nipple discharge (electrochemiluminescence method), and associations of these biomarkers with breast cancer prognosis were studied. Sixty cases of benign breast lesion were selected as a control group. Overall survival of breast carcinoma patients was evaluated. COX-2 expression was evaluated relative to clinicopathological features and CEA and CA153 levels, and its role in invasiveness was investigated. Results Among cases of invasive breast cancer, 72.7% (56/77) were COX-2 immunopositive, compared to 16.7% of benign lesions (χ2 = 66.745, P = 0.000) percentage of positive cells. COX-2 overexpression in breast cancer correlated positively with histological grade (II vs III; χ2 = 4.064, P = 0.043), lymph node metastasis (χ2 = 9.135, P = 0.003), and distant metastasis (χ2 = 8.021, P = 0.003). However, COX-2 expression did not correlate with age (≤ 50 vs 50 years) or tumor size (≤ 5 vs &gt; 5 cm) (χ2 = 0.081, P = 0.776 and χ2 = 3.702, P = 0.054, respectively). Among breast cancer patients, COX-2 overexpression in tumors also correlated with shorter overall survival (P &lt; 0.05). In brief, increased COX-2 expression correlates with worse prognosis and shorter overall survival. Malignant lesions were associated with significantly higher serum and nipple discharge levels of biomarkers, relative to benign lesions (P &lt; 0.05). These biomarkers were present at significantly higher levels in nipple discharge than in serum (P &lt; 0.05). Furthermore, significantly higher nipple discharge levels of CEA and CA153 were observed in COX-2-positive breast carcinoma patients, compared to COX-2-negative patients (P &lt;0.05). Shorter overall survival in cancer patients group related to COX-2 overexpression in tumors (P &lt; 0.05). Conclusion The study suggests that COX-2 overexpression correlates with poor clinicopathological parameters in breast cancers and might be an important biological marker of invasion and metastasis. The findings of the present study suggest that combined detection of COX-2 tissue expression and CEA and CA153 in serum and nipple discharge could facilitate clinical monitoring and diagnosis of metastasis in patients with breast cancer.

Relation between Carcinoembryonic Antigen Levels in Colon Cancer Tissue and Serum Carcinoembryonic Antigen Levels at Initial Surgery and Recurrence

Objectives: Carcinoembryonic antigen (CEA) is widely used for postoperative surveillance of colon cancer. Even if serum CEA is negative at initial surgery, it may turn positive at recurrence. We investigated the relation between serum CEA levels and the immunohistochemical staining status of CEA in the primary and resected metastatic tissues. Methods: Out of 224 patients with recurrent colon cancer between 1998 and 2012, we studied 46 patients in whom serum CEA levels were measured and immunohistochemical staining for CEA was possible in the primary and metastatic tissues. Results: The positive rate of serum CEA did not differ between initial surgery and recurrence, regardless of whether the cutoff value was set at 5 or 10 ng/ml (p = 0.829, p = 0.671). There was no relation between the CEA staining status and serum CEA level at initial surgery. However, the CEA staining status of metastatic tissue was significantly related to the serum CEA level at recurrence (p = 0.0046 and p = 0.0026). Conclusions: The immunohistochemical staining status of CEA in metastatic tissue is closely related to the serum CEA level. This finding suggests that serum CEA levels are influenced not only by the CEA production capacity of cancer cells but also by the ability of the surrounding tissue to release CEA into the blood.

Clinical relationship and the prognostic factor between serum carcinoembryonic antigen (CEA) and tissue CEA in colorectal cancer patients

Purpose: The aim of this study was to investigate the prognostic factor for elevating serum carcinoembryonic antigen (CEA) in patients with colorectal cancer and to identify clinical usefulness of tissue CEA. Methods: Two hundred and eighty-five patients with colorectal cancer were performed serum CEA tests before and after surgery. Also resected tumors were checked expressions pattern of tissue CEA. Clinicopathologic factors were classified according to patient factors, tumor factors and molecular factors. Patient factors included age, sex, underlying liver disease, smoking history and other cancer history. Tumor factors included tumor size, intestinal obstruction, pathologic T status, lymph node metastasis, tumor differentiation, lymphatic invasion, vascular invasion, perineural invasion. Results: Serum CEA level was markedly elevated in the cytoplasmic pattern of tissue CEA compared to membranous pattern of tissue CEA. As cancer stage progressed, serum CEA level was elevated, which was confined to cytoplasmic pattern of tissue CEA. Independent factors for the elevation of serum CEA by multivariate analysis included tumor size (≥5 cm) (P=0.042), complete intestinal Obstruction (P=0.023) and serum CA 19-9 (≥37 U/mL) (P=0.027). p53 overexpression (≥10%) was related to cytoplasmic pattern in tissue CEA (P=0.005). Conclusion: The tumor size and bowel obstruction are considered the main factors, which cause the leakage of intracellular CEA. And membranous patterns of tissue CEA can be used in Stage I colorectal cancer patients, as an indicator for early prognosis and recurrence. However, more studies of colorectal population are required for further evaluation.

Prognostic Significance of Carcinoembryonic Antigen Staining in Cancer Tissues of Gastric Cancer Patients.

The aim of this study was to assess the significance of the correlation among tissue carcinoembryonic antigen (CEA) expression with serum CEA (sCEA) levels and long-term survival to highlight the clinical prognostic significance of tissue CEA expression in gastric cancer patients. Immunohistological method and radioimmunoassay were used to assess tissue and sCEA expression, respectively. Univariate and multivariate analyses were performed to determine correlations, and the Kaplan-Meier method was used to investigate the prognostic significance. Our results demonstrate that tissue CEA in gastric cancer is significantly correlated with preoperative sCEA levels (p=0.031), depth of invasion (p=0.001), lymph node metastasis (p<0.001), distant metastasis (p=0.001), and TNM staging (p<0.001). The 5-year survival rates were 67.6, 53.9, and 40.1% for negatively, moderately, and intensely positively stained tissues (p<0.001), and 57.0 and 37.9% for serum with normal and elevated CEA expression (p=0.031). Multivariate analysis revealed that tissue CEA can be considered an independent prognostic factor. Further analysis illustrated that patients with negative expression in both tissue and serum had better prognosis compared with those positively expressing CEA in both tissue and serum and/or those positively expressing CEA in either tissue or serum (p<0.001). Our results also demonstrated that patients with negative tissue CEA staining and elevated sCEA expression had a better 5-year survival. Tissue CEA expression in gastric cancer is directly correlated with sCEA levels and long-term prognosis. Thus, tissue CEA expression can be considered as a useful biomarker to improve the interpretation of sCEA levels in predicting long-term survival.

Relation between carcinoembryonic antigen (CEA) production in colorectal cancer (CRC) tissue and serum CEA levels: Comparison between the time of recurrence and initial diagnosis.

561 Background: Because serum CEA often becomes positive before the diagnosis of recurrence, CEA is widely used for postoperative surveillance. Serum CEA is negative at initial diagnosis as well as at recurrence in some patients. We examined the relation between serum CEA levels and tissue CEA staining status both at initial surgery and at recurrence. Methods: Between 1998 to 2012, 1,306 patients (pts) with colon cancer (CC) underwent curative resection. Serum CEA levels were measured at initial surgery and at recurrence and immunohistochemical staining for CEA in primary and metastatic lesions was performed in 46 pts. Serum CEA levels of 10ng/mL or more were regarded as positive. Results: Serum CEA were positive in 17 pts (37%) at initial surgery and in 20 (43%) at recurrence. CEA staining was positive in primary lesions in 24 pts (52%) and metastatic lesions in 33 (72%). The positive rate was higher in metastatic lesions (p=0.053). Among pts in whom serum CEA was positive at initial surgery, CEA staining in primary lesion was positive in 12 pts (71%) and negative in 5 (29%). Among pts in whom serum CEA was negative, CEA staining in primary lesion was positive in 12 pts (41%) and negative in 17 (59%). Serum CEA at initial surgery was not related to CEA staining in primary lesion(p=0.0722). Among pts positive for serum CEA at recurrence, CEA staining in metastatic lesions was positive in 19 pts(95%) and negative in 1(5%). Among pts negative for CEA at recurrence, CEA staining in metastatic lesions was positive in 14 pts (54%) and negative in 12 (46%). Serum CEA at recurrence was significantly related to CEA staining in metastatic lesions (p=0.0026). Among 33 pts in whom CEA staining was positive at recurrence, serum CEA was negative in 14 (42%). Conclusions: In pts with recurrence of CC, there was no relation between the staining CEA status and serum CEA level at initial diagnosis. In contrast, these variables were significantly related at recurrence. However, 42% of pts with positive staining for CEA in metastatic lesions had negative serum CEA levels. Our findings suggest that factors besides the production of CEA by cancer cells are related to serum CEA levels.

Clinical validity of tissue carcinoembryonic antigen expression as ancillary to serum carcinoembryonic antigen concentration in patients curatively resected for colorectal cancer

Although serum carcinoembryonic antigen (CEA) level is prognostic in colorectal cancer, the prognostic role of tumour CEA expression is unclear. The aim of this study is to identify the prognostic and surveillance roles of tissue CEA expression along with serum CEA concentration in patients curatively resected for colorectal cancer. Between January and December 2003, 294 patients who underwent curative resection for colorectal cancer were included in the study. Correlation of tissue CEA expression with overall survival (OS), disease-free survival (DFS) and elevated serum CEA concentration at tumour recurrence were analysed. Tissue CEA expression was positive in 215 patients (73.1%). CEA expression was an independent prognostic factor for OS [hazard ratio (HR) = 2.537, 95% confidence interval (CI) = 1.065-6.042, P = 0.035] and DFS (HR = 3.090, 95% CI = 1.405-6.795, P = 0.005). Elevation of serum CEA at tumour recurrence was significantly lower in patients without than with tissue CEA expression (14.3 vs 57.6%, P = 0.045). Moreover, when patients were grouped according to a combination of serum CEA elevation and tissue CEA expression, those with tissue CEA expression and elevated serum CEA (group 3) had significantly poorer OS and DFS (P < 0.001 each) than those without CEA expression and elevated serum CEA (group 1) and those with either tissue CEA expression or elevated serum CEA (group 2). OS (P = 0.006) and DFS (P = 0.027) were both significantly greater in group 1 than in group 2. Tissue CEA expression is a prognostic factor in patients with colorectal cancer. Analysis of tissue CEA expression may be helpful in determining the clinical utility of serial measurements of serum CEA as surveillance in patients with curatively resected colorectal cancer.

Tissue carcinoembryonic antigen, calcium, copper and iron levels in cancerous lung patients.

Background and objectiveThe expression of various trace elements and markers in lung cancer is controversial. The aim of this study is to evaluate the presence of calcium (Ca), copper (Cu), iron (Fe) and carcinoembryonic antigen (CEA) in cancerous untreated lung tissues and to determine a possible association between these markers and lung cancer.MethodsFourty-eight cancerous lung tissue blocks, from Sultan Qaboos University Hospital, Sultanate of Oman, were studied. Fe, Ca, Cu, and CEA were demonstrated in the tissue blocks using Perl's Prussian blue, Von Kossa's, modified rhodanine and immunohistochemical staining methods, respectively.ResultsTwenty-three of 48 specimens showed positive Fe staining, 2 showed positive Ca staining and Cu was absent in all specimens. 93.7% expressed CEA in varying degree of positivity. 81.25% of these sections showed high expression of CEA.ConclusionTissue concentrations of trace elements were not elevated in lung cancer and therefore cannot be considered as a potential marker. Despite the low sensitivity and specificity of CEA as previously reported, tissue CEA should be considered as a potential marker in the evaluation of lung cancer.

Morphofunctional malignancy grading is a valuable prognostic factor for colorectal cancer

Novel strategies are needed to identify more efficient biomarkers to accurately diagnose prognose and improve the treatment outcome of colorectal cancer. To analyze the functional and morphological features of colorectal cancer to identify the neoplastic patterns that affect patient survival. Forty-five patients with colorectal cancer were followed for a minimum of 3 years. Blood levels of carcinoembryonic antigen (CEA) were measured by chemiluminescence and immunohistochemical analysis of tissue expression followed by computer-assisted image processing. Tumors were assigned to three morphofunctional classes. The morphofunctional classification was based on combination between histological differentiation and cell polarization. The functional characterization was based on the CEA cell polarization. The tissue polarization of CEA was classified in well-polarized, moderately polarized or nonpolarized cells. Morphofunctional staging was defined by the association between morphofunctional class (polarization and histological differentiation) and TNM by score given to each one classification. There was an association between increased CEA tissue expression and loss of histological differentiation (P = 0.01) or loss of polarization capacity (P = 0.03). There was a progressive increase in tissue CEA quantities in accordance with the proposed morphofunctional grading system. Plasma levels of CEA were increased in advanced tumor stages. Blood levels of CEA were increased in advanced morphofunctional stages (P = 0.001). There was a relationship between survival outcome and morphofunctional staging (P = 0.005). Morphofunctional staging is a valuable prognostic factor for colorectal cancer and it correlates with plasma CEA levels.

Urine carcinoembryonic antigen determination in urinary bladder bilharziasis predicts carcinoma in patients with premalignant lesions: Observation of 43 cases in Egypt

Both urinary bilharziasis and urothelial neoplasia are associated with increased production of tissue carcinoembryonic antigen (CEA). Urine and serum CEA were determined in 43 patients with urinary bladder carcinoma including 22 post bilharzial and 21 non-biharzial cases, in addition to 10 normal control cases. A significant increase was detected in both urine and serum CEA levels with bladder carcinoma compared to control cases. Urinary CEA was significantly elevated in 86% of bilharzial versus 62% in nonbilharzial bladder carcinoma. Only 10.5% of control cases had urinary CEA elevation. The mean urinary CEA in bilharzial was higher than that of nonbilharzial carcinoma, but the difference was not statistically significant. There was a definite relationship between urine CEA and the stage of malignancy; the higher the stage, the higher the level of urine CEA. No relationship could be detected between the stage of malignancy and serum CEA, or between the grades of malignancy and urine or serum CEA levels. In conclusion, urinary CEA is more useful than serum CEA in the early detection of bilharziasis-associated urothelial carcinoma.