1048

CEACAM5

carcinoembryonic antigen-related cell adhesion molecule 5;CEACAM5;carcinoembryonic antigen-related cell adhesion molecule 5

meconium antigen 100

19q13.1-q13.2

protein-coding

The value of serum tumour markers in the prognosis of patients with breast cancer is controversial. This prospective study in Yazd, Islamic Republic of Iran, assessed the value of the tumour markers carcinoembryonic antigen (CEA) and cancer antigen (CA) 15-3 in 159 patients with primary breast cancer. CEA and CA15-3 assays (mean 14 per patient) were performed at diagnosis, end of surgery and chemotherapy and every 3 months in the first 2 years and every 6 months in second 2 years of the follow-up period. During follow-up, 33 patients (20.8%) presented symptomatic metastasis. A significant relationship was seen between metastasis status and positive CEA and CA15-3 levels. The sensitivity and specificity were 66.7% and 98.4% for CEA respectively and 84.8% and 91.3% for CA15-3 respectively. Optimum cut-offs were 4.95 ng/mL and 30.5 U/mL for CEA and CA15-3 respectively.

It has been suggested that carcinoembryonic antigen (CEA) enhances metastatic seeding of colon cancer cells due to its homo- and heterophilic binding properties. Our recent finding that endogenous CEA protects colon cancer cells against apoptosis suggests a more complex role of CEA in cancer progression. In this study we compared the in vitro effects of endogenous CEA on tumor cell aggregation and cell cycle regulation of human HT29 colon cancer cells with the corresponding in vivo effects, i.e. tumor cell seeding and formation of metastatic lesions. Stable expression of CEA targeted ribozymes (Rz) under control of a tet-off promoter system allowed regulation of CEA levels on the mRNA and protein level by 50%. Downregulation of CEA levels inhibited tumor cell aggregation by 70%. In accordance with previous studies, reduction of CEA levels increased in vitro the apoptotic rate and reduced colony formation by 30% to 50%. To determine the in vivo effect of CEA-dependent aggregate formation and its growth regulating role under apoptotic stress, HT29 cells with high and low CEA levels, respectively, were injected into nude mice. Immunostaining of lung microsections revealed similar numbers of tumor cells one hour after injection. 24 h later virtually all cells were removed from the lung in both groups. However, after 6 weeks all doxycycline treated mice (Rz off = CEA high) showed 14.5 +/- 4.6 metastatic lung lesions/mouse while 0.2 +/- 0.2 lesions/mouse appeared in the untreated group (Rz on = CEA low) (P < 0.001). Our study demonstrates a multifunctional role of CEA and indicates a prometastatic role of CEA independent of its adhesive function possibly due to its anti-apoptotic function.

BACKGROUND AND OBJECTIVE: Oxaliplatin (OXA)-induced carcinoembryonic antigen (CEA) surge was reported to be associated with a clinical benefit. The aim of this study was to investigate the phenomenon of CEA surge in irinotecan-based chemotherapy. METHODS: We retrospectively reviewed 132 patients with metastatic colorectal cancer treated with irinotecan-based chemotherapy. Incidence of a CEA surge and chemotherapy efficacy were investigated. RESULTS: Eleven of 99 eligible patients (11.1%) had CEA surges. None of the 11 patients showed progressive disease (four had a partial response, seven had stable disease). CONCLUSION: A CEA surge can be induced by irinotecan-based chemotherapy. An early increase in CEA after irinotecan-based chemotherapy does not usually indicate progression of disease and failure of therapy, and should not lead to a change of chemotherapy.

BACKGROUND: The prognostic/predictive value of potential vascular endothelial growth factor (VEGF) signalling biomarkers was evaluated retrospectively using samples from two randomized Phase III studies (HORIZON II and III) investigating cediranib in metastatic colorectal cancer (mCRC). METHODS: Baseline levels of VEGF, soluble VEGF receptor-2 (sVEGFR-2) and carcinoembryonic antigen (CEA) were measured in plasma/serum samples collected from patients participating in HORIZON II (n=860; FOLFOX/XELOX plus cediranib 20 mg (n=502) or placebo (n=358)) and HORIZON III (n=1422; mFOLFOX6 plus cediranib 20 mg (n=709) or bevacizumab (n=713)). Median biomarker baseline levels determined cutoff values for the patient subgroups. RESULTS: Baseline data were available for 88-97% of patients/study (>2000 patients). In both the studies, high baseline VEGF and CEA were associated with worse outcomes for progression-free survival (PFS) and overall survival (OS) independent of treatment (HORIZON II OS: VEGF, hazard ratio (HR)=1.35 (95% confidence interval (CI): 1.12-1.63); CEA, HR=1.63 (1.36-1.96); HORIZON III OS: VEGF, HR=1.32 (1.12-1.54); CEA, HR=1.50 (1.29-1.76)). sVEGFR-2 was not prognostic for PFS/OS. Baseline VEGF and CEA were not predictive for PFS/OS outcome to cediranib treatment; low sVEGFR-2 was associated with a trend towards improved cediranib effect in HORIZON II. CONCLUSION: Baseline VEGF and CEA levels were treatment-independent prognostic biomarkers for PFS and OS in both the studies.

In patients with metastatic colorectal cancer (mCRC), radiological imaging represents the current standard to evaluate the efficacy of chemotherapy. However, with growing knowledge about tumor biology, other diagnostic tools become of interest which can supplement radiology. The aim of the present study was to examine the correlation of tumor and serum markers with radiological imaging in patients with mCRC receiving first-line therapy. Patients were included if tumor (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9)) and serum marker (lactatdehydrogenase (LDH), gamma-glutamyltransferase (gammaGT), alkaline phosphatase (AP), C-reactive protein (CRP), leucocyte count (WBC), hemoglobin (Hb)) levels were available at baseline and at least two times during treatment. The decline and increase of tumor and serum markers over time were approximated for each patient by estimating slopes depending on the radiological assessment. A linear mixed effects multiple regression model for each subject was used to evaluate the intra-class correlation of these slopes modeling tumor and serum marker changes with radiological imaging. Data of 124 patients (41 female, 83 male; median age 62.9 years, range 27-85) who received first-line chemotherapy for mCRC from 11/2007 to 04/2010 were analyzed retrospectively. CEA level slopes (n = 49; slopes = 102) differed between radiologically determined progressive disease (PD) and partial response (PR) (p = 0.005) and between PD and stable disease (SD) (p = 0.042). CA 19-9 level slopes (n = 57; slopes = 127) also showed a significant difference between PD and PR (p = 0.002) and PD and SD (p = 0.058). Furthermore, CRP slopes (n = 62; slopes = 134) differed significantly between PD and PR (p = 0.009). For LDH, ALP, gammaGT, Hb, and WBC, no correlations were observed. The results indicate the correlation of the tumor markers CEA, CA 19-9, and the serum marker CRP with radiological imaging in patients with mCRC receiving first-line chemotherapy. Further data analyses would be helpful to develop a predictive model for tumor response based on an early tumor marker increase or decrease.

The purpose of this study was to determine whether lysyl oxidase (LOX) is a useful marker of metastasis in gastric cancer (GC) patients in combination with tumor markers carcino-embryonic antigen (CEA), carbohydrate antigen 724 (CA724), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125). There were 215 GC patients (67 without metastasis, 102 with lymph node metastasis, and 46 with peritoneal metastasis) who presented to the Affiliated cancer Hospital of Guangxi Medical University between May 2009 and November 2012 that were enrolled in this study. The LOX expression level and the serum concentration of the four tumor markers were evaluated preoperatively. All patients underwent computed tomography (CT) and ultrasonography (US) before surgery. Statistical analysis, including receiver operating characteristic (ROC) curve analysis, area under the curve (AUC) analysis, and logistic regression analysis, was performed to evaluate the diagnostic value of these markers in predicting metastasis in GC. For predicting lymph node metastasis in GC, the sensitivity of LOX, CEA, CA724, CA199, and CA125 was 44.12, 12.75, 21.57, 23.53, and 15.69 %, respectively, and increased to 79.41 % in combination. For predicting peritoneal metastasis in GC, the sensitivity of these markers was 56.52, 23.91, 34.78, 36.96, and 34.78 %, respectively, and increased to 91.30 % in combination. Combining LOX with CEA, CA724, CA199, and CA125 could increase the sensitivity of predicting lymph nodes metastasis and peritoneal metastasis in GC. Surgeons can use these markers to determine the best treatment options for patients. Additional large-scale, prospective, multicenter studies are urgently needed to further confirm the results of this study.

The human carcinoembryonic antigen (CEA) is a cell adhesion molecule involved in both homotypic and heterotypic interactions. The aberrant overexpression of CEA on adenocarcinoma cells correlates with their increased metastatic potential. Yet, the mechanism(s) by which its adhesive properties can lead to the implantation of circulating tumor cells and expansion of metastatic foci remains to be established. In this study, we demonstrate that the IgV-like N terminal domain of CEA directly participates in the implantation of cancer cells through its homotypic and heterotypic binding properties. Specifically, we determined that the recombinant N terminal domain of CEA directly binds to fibronectin (Fn) with a dissociation constant in the nanomolar range (K(D) 16 +/- 3 nM) and interacts with itself (K(D) 100 +/- 17 nM) and more tightly to the IgC-like A(3) domain (K(D) 18 +/- 3 nM). Disruption of these molecular associations through the addition of antibodies specific to the CEA N or A(3)B(3) domains, or by adding soluble recombinant forms of the CEA N, A(3) or A(3)B(3) domains or a peptide corresponding to residues 108-115 of CEA resulted in the inhibition of CEA-mediated intercellular aggregation and adherence events in vitro. Finally, pretreating CEA-expressing murine colonic carcinoma cells (MC38.CEA) with rCEA N, A3 or A(3)B(3) modules blocked their implantation and the establishment of tumor foci in vivo. Together, these results suggest a new mechanistic insight into how the CEA IgV-like N domain participates in cellular events that can have a macroscopic impact in terms of cancer progression and metastasis.

The prognostic value of p53 and c-erbB-2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non-small cell lung cancer (NSCLC) patients with resectable tumors. Four end-points were used: lung cancer death, first relapse (either locoregional or metastasis), loco-regional recurrence and metastasis development. Standard statistical survival methods (Kaplan-Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose-response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lung-cancer recurrence. They can add useful information regarding the complex nature of prognosis.

BACKGROUND: Central nervous system is a common site of metastasis in NSCLC and confers worse prognosis and quality of life. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF), serum CEA levels, and EGFR and HER2 tissue-expression in brain metastasis (BM) and overall survival (OS) in patients with advanced NSCLC. METHODS: In a prospective manner, we studied 293 patients with NSCLC in IIIB-IV clinical stage. They received standard chemotherapy. CEA was measured prior to treatment; EGFR and HER2 were evaluated by immunohistochemistry. BM development was confirmed by MRI in symptomatic patients. RESULTS: BM developed in 27, and 32% of patients at 1 and 2 years of diagnosis with adenocarcinoma (RR 5.2; 95% CI, 1.002-29; p = 0.05) and CEA > or = 40 ng/mL (RR 11.4; 95% CI, 1.7-74; p < 0.01) as independent associated factors. EGFR and HER2 were not statistically significant. Masculine gender (RR 1.4; 95% CI, 1.002-1.9; p = 0.048), poor performance status (RR 1.8; 95% CI, 1.5-2.3; p = 0.002), advanced clinical stage (RR 1.44; 95% CI, 1.02-2; p = 0.04), CEA > or = 40 ng/mL (RR 1.5; 95% CI, 1.09-2.2; p = 0.014) and EGFR expression (RR 1.6; 95% CI, 1.4-1.9; p = 0.012) were independent associated factors to worse OS. CONCLUSION: High CEA serum level is a risk factor for BM development and is associated with poor prognosis in patients with advanced NSCLC. Surface expression of CEA in tumor cells could be the physiopathological mechanism for invasion to CNS.

Increased expression of cell adhesion molecule CD44v6, integrin-beta1, carbohydrate antigen 199 (CA199), and carcinoembryonic antigen (CEA) are closely associated with the progression and metastasis of numerous cancers. In this study, peripheral blood mononuclear cell (PBMC) and serum samples were collected from 37 pancreatic cancer patients and 12 healthy people. A novel triplex TaqMan real-time reverse transcription polymerase chain reaction assay was used to measure the expression levels of CD44v6 and integrin-beta1 gene in PBMCs, while chemiluminescence and enzyme-linked immunosorbent assay were used to measure the levels of CA199 and CEA expression in serum. The results showed that both the levels of CD44v6 and integrin-beta1 expression had significant correlation with clinical stage, lymph node, and liver metastasis of pancreatic cancer (P < 0.05). Age, tumor size, tumor differentiation, clinical stage, lymph nodes, and liver metastasis were significantly associated with the levels of CA199 and CEA expression (P < 0.05). The levels of CD44v6, integrin-beta1, CA199, and CEA expression in the patients prior cryosurgery and chemotherapy were significantly higher than those in the control group (P < 0.05), whereas no significant difference was found between the patients 1 month post cryosurgery and control group (P > 0.05). The expression levels of CD44v6, integrin-beta1, CA199, and CEA in the patients 1 month post cryosurgery were significantly lower than those in the patients prior cryosurgery (P < 0.05). Interestingly, no significant difference was found for the CD44v6, integrin-beta1, CA199, and CEA levels between the patients prior and post-chemotherapy (P > 0.05). The higher expression of CD44v6, integrin-beta1, CA199, and CEA are closely related to the progression and metastasis of pancreatic cancer and may play a important role in the curative evaluation of cryosurgery of pancreatic cancer.