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Background
CEA stands for carcinoembryonic antigen, a protein normally found in the fetal tissues of the intestines, pancreas, and liver. Note that benign, non cancerous conditions may also cause elevations of this protein.
DISEASE ASSOCIATIONS CHARACTERIZATION Common Associations Colon, Metastatic Breast CA Less Common Alcoholic cirrhosis, hepatitis, ulcerative colitis, Crohn's disease
CLINICAL UTILITY CHARACTERIZATION COLON CANCER Elevated CA19-9 as the most significant prognostic factor in advanced colorectal carcinoma.
Kouri M, Pyrhonen S, Kuusela P.
Department of Radiotherapy and Oncology, Helsinki University Central Hospital, Finland.
J Surg Oncol 1992 Feb;49(2):78-85 Abstract quote
Tumor markers such as carcinoembryonic antigen (CEA) and CA19-9 were analyzed as response indicators and prognostic factors in advanced colorectal carcinoma.
Eighty-five patients participated in a phase II chemotherapy study from October 1984 to July 1990. A three-drug schedule was administered including low dose epirubicin and sequential methotrexate 5-fluorouracil, followed by leucovorin rescue. Serum specimens for CEA and CA19-9 were obtained prior to the initiation of chemotherapy, and subsequently at 4-6 weeks' intervals.
In univariate analysis Karnofsky, the site of the primary tumor, the extent of metastases, the presence of abdominal or liver metastases, serum CEA (cut-off of 20 micrograms/l), and CA19-9 levels correlated with survival.
In stepwise multivariate analysis an elevated CA19-9 level, a poor Karnofsky, and the presence of liver metastases were independent adverse prognostic factors. Tumors originating from the left colon had a better prognosis than the others. This was related to a higher response rate in this patient group. Serum CA19-9 level was the most significant prognostic factor whether it was entered as a continuous or as a dichotomized variable into the model. The median survival of patients with a normal CA19-9 level was 30.0 months (lower 95% confidence interval: 16.4 months; upper limit was not calculable), and with an elevated CA19-9 value 10.3 months (8.0-12.6 months, 95% confidence interval). Five of 85 patients had a complete response and 20 a partial response, the overall response rate being 29%.
When compared with tumor shrinkage, "CEA response" and "CA19-9 response" had a sensitivity of 84% and 88% and specificity of 77% and 67%, respectively. In conclusion, serum CEA value seems to be the best tumor marker for response prediction, while CA19-9 level is one of the best available prognostic indicators in advanced colorectal carcinoma.
Evaluation of serum carcinoembryonic antigen monitoring in the follow-up of colorectal cancer patients with metastatic lymph nodes and a normal preoperative serum level.
Tobaruela E, Enriquez JM, Diez M, Camunas J, Muguerza J, Granell J.
Department of General Surgery, Principe de Asturias University Hospital, Alcala de Henares, Madrid, Spain.
Int J Biol Markers 1997 Jan-Mar;12(1):18-21 Abstract quote
The value of serial serum carcinoembryonic antigen (CEA) assay in the follow-up of colorectal cancer patients with metastatic lymph nodes and normal (< or = 5 ng/ml) preoperative CEA levels, was examined in this study.
Thirty-eight patients were studied and compared with 22 patients with elevated CEA levels. The overall sensitivity of CEA for the diagnosis of recurrence was 36%. Postoperative CEA was strongly influenced by the site of recurrence. CEA monitoring showed the best results in patients who developed hepatic metastases (sensitivity 60%, specificity 94%, positive predictive value 60%, and negative predictive value 94%), and was ineffective for the detection of locoregional or pulmonary metastases.
The results indicate that elevation of CEA in the postoperative course of these patients is an indicator of the presence of hepatic metastases. Postoperative CEA monitoring should not be omitted in Dukes C patients with normal preoperative levels, and is more reliable for the detection of liver metastases.
The significance of CEA, CA19-9 and CA72-4 in the detection of colorectal carcinoma recurrence.
Holubec L Jr, Topolcan O, Pikner R, Pecen L, Vaclavickova J, Wirthova M, Molacek J, Stieber P, Holdenrieder S, Sen LH, Finek J.
2nd Dept. of Internal Medicine, Clarles University Hospital, E. Benese 13, 30599 Pilsen, Czech Republic.
Anticancer Res 2000 Nov-Dec;20(6D):5237-44 Abstract quote
The significance of CEA, CA19-9 and CA72-4 was evaluated the for early detection of disease recurrence, on the basis of retrospective evaluation of routine data in patients with colorectal carcinoma. They also considered the dependence of the results of these data analyses on the definition of groups of patients, both with no evidence of disease (NED) and with recurrence of disease (RD).
PATIENTS AND METHODS: From January 1994 to March 1999 serum levels of CEA, CA19-9 and CA72-4 were determined in the follow-up of 517 patients with colorectal cancer and compared with the retrospectively confirmed clinical status of the patients.
RESULTS: CEA and CA19-9 showed comparable sensitivities in the detection of locoregional recurrence of colorectal carcinoma, whilst the sensitivity of CA72-4 was considerably lower. CEA is an optimal marker for detecting distant metastases, in particular liver metastases, since its sensitivity considerably exceeds the sensitivities of the other two monitored markers.
CONCLUSION: Using routine data required detailed analysis and clear definitions of groups of patients with NED and RD. The following conclusions for the evaluation of data were drawn from this analysis: a) Tumor marker cut-off values and sensitivities related to 95% specificity of remission values depended strongly on the given definition of the groups of patients with NED and RD. b) The patient group with NED is best characterized as the group of patients who never developed progression and where all the values which were assessed within a period shorter than six months from the end of therapy and follow-up, or less than six months before progression, death, or before the last marker assessment in the patient, were excluded. c) For the optimal characterisation of the group of patients with RD it is recommended only to consider values obtained during the first progression, after the period of complete post-operative or post-therapeutic remission. d) These conclusions refer not only to routine data, where this correction represents a condition for reliable evaluation, but also to any research done, since they ensure complete homogeneity of the group and mutual comparability of the results.
Multivariate analysis of the prognostic value of CEA and CA 19-9 serum levels in colorectal cancer.
Reiter W, Stieber P, Reuter C, Nagel D, Lau-Werner U, Lamerz R.
Institute of Clinical Chemistry, Klinikum of the University Munich, Grosshadern, Germany.
Anticancer Res 2000 Nov-Dec;20(6D):5195-8 Abstract quote
Carcinoembrionic Antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are the most commonly used tumor-associated antigens in the management of patients with colorectal cancer. The aim of this study was to evaluate the prognostic value of preoperative serum levels of CEA and/or CA 19-9 and the classical prognostic factors (age, sex, tumor infiltration and staging) in 495 patients.
PATIENTS AND METHODS: The retrospective study was performed on frozen sera (stored at -70 degrees C) of patients with histologically proven colorectal cancer. Survival function estimates were calculated (Kaplan-Meier). The patients were separated into two groups according to the preoperative marker levels. Cut-off levels calculated at a specificity of 100% versus healthy individuals were used: < 4 ng/mL versus > or = 4 ng/mL for CEA and < 60 U/mL versus > or = 60 U/mL for CA 19-9. Survival curve differences were assessed using the log-rank-test. Mulivariate Cox's proportional hazard regression analysis was performed to examine the association between tumor marker levels and survival time. Classical prognostic factors such as age, sex, tumor infiltration, tumor stage (Dukes' classification) were included as covariants. The mantel-Haenszel method was used to assess the survival rate of patients with colorectal carcinoma and high versus low levels of tumor-associated antigens according to tumor stages.
RESULTS: The Dukes' stages (log-rank chi-square = 231.9; p < 0.0001) represent the best prognostic factor besides the preoperative values of CA 19-9 (log-rank chi-square = 162.5). CEA shows a log-rank chi-square of 71.4. Thus, CEA and CA 19-9 can be used to discriminate two groups of patients with significantly different survival times (p < 0.0001). The importance of different parameters in providing additional prognostic information was evaluated by multivariate analysis. Only items of statistically significant prognostic relevance (univariate analysis) were used for this analysis. Estimated relative risks of death adjusted for tumor stage were 5.5 considering Dukes' stage A versus Dukes' stage B/C and Dukes' stage B/C versus Dukes' stage D, respectively, and an increasing relative risk of 27.5 for Dukes' stage A versus Dukes' stage D (p < 0.001). The relative risk for preoperative CA 19-9 serum concentrations (> or = 60 U/mL versus < 60 U/mL) was 2.3 (p < 0.001) and for preoperative CEA concentrations (> or = 4 ng/mL versus < 4 ng/mL) 1.4 (p < 0.07). For CEA the 2-year survival rates in the group of patients with preoperative serum concentrations > 4 ng/mL versus < 4 ng/mL and Dukes' stage D were 16% versus 38%, in Dukes' stage B/C 73% versus 91% and in Dukes' stage A 100% versus 98%. For CA 19-9 the 2-year survival rates in the group of patients with preoperative serum concentrations > or = 60 U/mL versus < 60 U/mL and Dukes' stage D were 10% versus 39%, whilst in Dukes' stage B/C 58% versus 87%. In the group of patients with Dukes' stage A with serum levels > or = 60 U/mL a 2-years survival rate of 100% was found.
CONCLUSION: The postoperative Dukes' classification represents the best prognostic information besides the preoperative values of CA 19-9. The predictive information provided by preoperative CA 19-9 serum levels is independent from that obtained by the other factors investigated. Only Dukes' classification and CA 19-9 levels showed statistical significance (p < 0.001).
CEA mRNA identification in peripheral blood is feasible for colorectal, but not for gastric or pancreatic cancer staging.
Piva MG, Navaglia F, Basso D, Fogar P, Roveroni G, Gallo N, Zambon CF, Pedrazzoli S, Plebani M.
Department of Laboratory Medicine, University of Padua, Italy.
Oncology 2000 Nov;59(4):323-8 Abstract quote
OBJECTIVE: It has been suggested that the molecular identification of cancer cells in the circulation may be useful in predicting the presence of micrometastasis in several cancer types. The aim of the present study was therefore to assess the feasibility of CEA mRNA identification in blood for diagnosing and staging colorectal, gastric and pancreatic cancer.
METHODS: We studied 16 control subjects, 69 patients with colorectal (CRC), 30 with gastric (GC), 27 with pancreatic cancer (PC) and 8 with benign diseases of the pancreatobiliary tree. At diagnosis CEA mRNA was identified in peripheral blood by means of a RT-PCR procedure.
RESULTS: The specificity of this test in control subjects was 94%, and its sensitivity in identifying CRC, GC and PC were 34, 37 and 41%, respectively. False-positive findings were recorded in 25% patients with benign diseases. No association was found between CEA mRNA and stage in patients with GC or PC. In CRC patients, positive CEA mRNA findings were correlated with local spread (chi(2) = 14.6, p<0.01), lymph node (chi(2) = 18.95, p<0.001) and distant metastasis (chi(2) = 11.3, p<0.001). In these cases, CEA mRNA, but not CEA, was entered in stepwise discriminant analysis to classify the presence of lymph node metastasis.
CONCLUSIONS: The molecular detection of micrometastasis in the blood by means of CEA mRNA identification is feasible for colorectal, but not for gastric or pancreatic cancer staging. Further studies are needed in order to define the clinical utility of this marker also in follow-up protocols.
The carcinoembryonic antigen and its prognostic impact on immunocytologically detected intraperitoneal colorectal cancer cells.
Vogel I, Francksen H, Soeth E, Henne-Bruns D, Kremer B, Juhl H.
Department of Surgery, Christian-Albrechts University, Kiel, Germany.
Am J Surg 2001 Feb;181(2):188-93 Abstract quote
BACKGROUND: Carcinoembryonic antigen (CEA) has been suggested to promote colon cancer progression. In this study we analyzed the prognostic impact of CEA expression on intraperitoneally detected single colon cancer cells.
METHODS: Peritoneal lavage samples of 135 colorectal cancer patients were immunocytologically analyzed, including a staining of cellular CEA; serum CEA levels were measured; and 5-year survival rates were calculated according to immunocytological findings and CEA expression.
RESULTS: The worst survival rate of 20% was found in patients suffering from CEA-expressing intraperitoneal tumor cells (P = 0.0006). The prognostic impact of an intraperitoneal tumor cell finding significantly increased when serum CEA levels were elevated: only 23% survived 5 years in contrast to a 85% 5-year survival rate of patients who neither had signs of dissemination nor showed elevated serum CEA values (P = 0.0010).
CONCLUSIONS: This study shows that the determination of CEA expression improves the prognostic impact of an intraperitoneal tumor cell finding.
Carcinoembryonic antigen and CA19-9: implications of quantitative marker measurement in tissues for prognosis of colorectal cancer.
Gebauer G, Muller-Ruchholtz W.
Department of Molecular and Cell Biology, Sidney Kimmel Cancer Center, San Diego, CA 92121-1123, USA.
Cancer Detect Prev 2001;25(4):344-51 Abstract quote
Measurement of tumor markers in serum of colorectal cancer patients after surgery is a sensitive method in early diagnosis of systemic spread of tumor cells. Moreover, prognostic association of carcinoembryonic antigen (CEA) content in serum at the time of surgery is well known. However, fairly unclear is whether quantitative content of CEA and CA19-9 in cancer tissue and adjacent normal mucosa of colorectal cancer patients is correlated to prognosis.
Concentrations of CEA and CA]9-9 were analyzed simultaneously in serum, cancer tissue, and normal colonic mucosa of 41 colorectal cancer patients operated for cure. Follow-up data were available for up to 82 months (median, 47 months) after surgery. During the follow-up period, 20 patients had a tumor recurrence, and all these patients died of metastatic disease. Using the median concentration of CEA and CA19-9 in tissues as a cut-off, no difference in overall and disease-free survival was observed between patients with elevated or normal CEA or CA19-9 concentrations in tumor tissue. However, in adjacent histologically normal mucosa, elevated CEA content was associated with significantly shorter overall survival (P = .0385) and disease-free survival (P = .0141) but not CA19-9 content. Despite the unknown biological function of tumor markers in malignant disease, measurement of tumor-associated antigens in colorectal tissues can become an interesting prognostic marker.
Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful?
Duffy MJ.
Department of Nuclear Medicine, St Vincent's University Hospital, Dublin 4, Ireland.
Clin Chem 2001 Apr;47(4):624-30 Abstract quote
BACKGROUND: Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers worldwide. Its main application is mostly in gastrointestinal cancers, especially in colorectal malignancy. Although in use for almost 30 years, the clinical value of CEA in colorectal cancer is still not clear.
METHODS: The literature relevant to the clinical value of CEA in colorectal cancer was reviewed. Particular attention was paid to studies involving metaanalyses and guidelines issued by Expert Panels.
RESULTS: Although of little use in detecting early colorectal cancer, high preoperative concentrations of CEA correlate with adverse prognosis. Serial CEA measurements can detect recurrent colorectal cancer with a sensitivity of approximately 80%, a specificity of approximately 70%, and can provide a lead time of approximately 5 months. CEA is the most frequent indicator of recurrence in asymptomatic patients and currently is the most cost-effective test for the preclinical detection of resectable disease. CEA is most useful for the early detection of liver metastasis in patients with diagnosed colorectal cancer. Overall, however, little evidence is available that monitoring of all patients with diagnosed colorectal cancer leads to enhanced patient outcome or quality of life.
CONCLUSIONS: Currently, the most useful application of CEA is in the detection of liver metastasis from colorectal cancers. Because of the relative success of surgery in resecting hepatic metastases, serial determinations of the marker are recommended for detecting cancer spread to the liver. In the future, preoperative concentrations of CEA may be included with the standard staging procedures for assessing prognosis.
High preoperative serum carcinoembryonic antigen predicts metastatic recurrence in potentially curative colonic cancer: results of a five-year study.
Wiratkapun S, Kraemer M, Seow-Choen F, Ho YH, Eu KW.
Department of Colorectal Surgery, Singapore General Hospital, Singapore.
Dis Colon Rectum 2001 Feb;44(2):231-5 Abstract quote
INTRODUCTION: Serum carcinoembryonic antigen is used mainly for tumor follow-up to detect recurrence of colonic cancer. However, raised preoperative carcinoembryonic antigen levels may be helpful for the identification of understaged cases and of patients meriting more intensive preoperative and postoperative diagnostic workup.
METHODS: From a prospectively collected database, the data on 261 patients who had curative colonic carcinoma with a minimal follow-up of five years and who had preoperative carcinoembryonic antigen levels assessed were retrieved and analyzed. Outcome parameters were local and/or distant recurrence and time to recurrence. These parameters were correlated with Dukes staging and preoperative carcinoembryonic antigen levels.
RESULTS: The cumulative disease-free survival of patients with a preoperative carcinoembryonic antigen level within the normal range was significantly better than that of those whose carcinoembryonic antigen was 5 ng/ml or more (P = 0.001). No patient with carcinoembryonic antigen levels less than 1 ng/ml developed metastatic recurrence. Twenty-three percent of all patients with a raised carcinoembryonic antigen above 5 ng/ml compared with 2.1 percent of patients with carcinoembryonic antigen below 5 ng/ml developed a metastasis at two years. At five years, these figures were 37.2 percent and 7.5 percent, respectively. Dukes staging and carcinoembryonic antigen levels were found to be directly correlated (P < 0.001) when all patients were included. Carcinoembryonic antigen of more of 15 ng/ml was found to be a significant adverse prognostic indicator for disease-free survival irrespective of Dukes staging (P < 0.02). Raised carcinoembryonic antigen levels predicted distant metastatic recurrence (P < 0.001) but did not predict local recurrence (P = 0.72).
CONCLUSIONS: High preoperative carcinoembryonic antigen levels above 15 ng/ml predicted an increased risk of metastatic recurrence in potentially curative colonic cancer and may indicate undetectable disseminated disease. Preoperative carcinoembryonic antigen levels predict understaging and the possibility of distant recurrence. Such patients may therefore be selected for adjuvant therapy where indicated. Therefore, carcinoembryonic antigen is complementary to conventional Dukes staging for the prediction of recurrence and survival.
PANCREATIC CANCER Clinical usefulness of CA-19-9 in pancreatic carcinoma.
Nakao A, Oshima K, Nomoto S, Takeda S, Kaneko T, Ichihara T, Kurokawa T, Nonami T, Takagi H.
Department of Surgery II, Nagoya University School of Medicine, Japan.
Semin Surg Oncol 1998 Jul-Aug;15(1):15-22 Abstract quote
Preoperative and postoperative serum levels of carbohydrate antigen-(CA)19-9 in 148 patients with carcinoma of the pancreas were studied.
All 18 patients with carcinoma of the pancreas of Stage I, II, and III were resectable, and their pre-operative serum levels of CA-19-9 were under 1,344 U/ml. Pre-operative serum levels of CA-19-9 in patients with Stage IV ranged widely between 5 and 32,240 U/ml. The postoperative survival rate was significantly superior in patients (n = 15) whose CA-19-9 pre-operative serum levels were less than 2,000 U/ml compare to those (n = 64) whose levels were over that level. Fifteen resectable patients who showed serum levels of CA-19-9 over 2,000 U/ml pre-operatively died within 2 years postoperatively due to recurrence, especially by liver metastasis in spite of aggressive surgery. I
ntraoperative quick immunostaining of CA-19-9 and carcinoembryonic antigen (CEA) was useful to diagnose intrapancreatic carcinoma development on frozen sections of cut margin of the pancreas and also useful in abdominal washing cytology combined with conventional staining.
GASTRIC CANCER The prognostic value of preoperative serum levels of CEA and CA19-9 in patients with gastric cancer.
Kodera Y, Yamamura Y, Torii A, Uesaka K, Hirai T, Yasui K, Morimoto T, Kato T, Kito T.
Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan.
Am J Gastroenterol 1996 Jan;91(1):49-53 Abstract quote
OBJECTIVES: The clinical significance of preoperative serum levels of tumor markers CEA and CA19-9 was evaluated in gastric cancer patients.
METHODS: Serum levels of CEA and CA19-9 were measured in 663 patients with gastric cancer who underwent laparotomies over a recent 4-yr period (1990-1993). The correlations between the serum levels of tumor markers and several clinicopathological factors were evaluated by univariate analysis. The significance of the tumor markers as prognostic factors was assessed by multivariate analysis.
RESULTS: The positivity rates of CEA and CA19-9 were 16.6% and 16.0%, respectively. The positivity of CEA correlated well with the sex of the patients, hepatic, peritoneal, and nodal metastases and the depths of tumors, but it correlated weakly with a tumor's histological type. The positivity of CA19-9 correlated well with various forms of metastases, depths, and tumor size. A significant in prognosis was observed between patients positive and negative for CA19-9 among those undergoing R0 resection. Multivariate analysis also revealed that serum CA19-9 was better than CEA as a prognostic factor.
CONCLUSIONS: CA19-9 in the preoperative sera is a good prognostic factor in gastric cancer patients, although tumor markers continue to have only limited diagnostic usefulness.
BREAST CANCER Decision Making Using Postoperative CEA and CA 15-3 for Detection of Breast Cancer Recurrence.
Okamoto T, Obara T, Izuo M, Ito Y, Yamashita T, Tanaka R, Kanbe M, Hirose K.
Department of Endocrine Surgery, Tokyo Women's Medical College, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan.
Breast Cancer 1995 Oct 31;2(2):127-131 Abstract quote
To determine the clinical implications of postoperative levels of serum carcinoembryonic antigen (CEA) and CA 15-3 as follow-up parameters for breast cancer, a retrospective study was conducted on 157 patients who underwent curative surgery for breast cancer.
Twenty-three patients had recurrences and 134 patients were without recurrence for more than one year after measuring the tumor marker. The receiver operating characteristic (ROC) curves indicated that CA 15-3 performed more accurately than CEA in discriminating between patients with recurrence (n = 23) and those without (n = 134). Of 23 patients with recurrence, CEA was elevated above the normal range (<2.9 ng/ml) in 32% and CA 15-3 was elevated above the normal range (> 20U/ml) in 67%. The elevation of the markers preceded the clinical appearance of metastases in 2 patients for CEA and in 5 patients for CA 15-3. False positive rates for CEA and CA 15-3 in the 134 patients without recurrence were 4% and 10%, respectively. Nevertheless, these rated became 0% when the cut-off values were doubled.
When the postoperative serum level of either CEA or CA 15-3 exceeds twice the upper limit of the normal range or when, in patients with unfavourable prognostic characteristics (node positive or large tumor), either of these values is between the upper limit of the normal range and double the value, recurrent breast cancer must be assumed. For such patients, further investigations with high-sensitivity radiographic modalities are warranted because early treatment may be able to provide survival benefit.
C-erbB-2, CEA and CA 15.3 serum levels in the early diagnosis of recurrence of breast cancer patients.
Molina R, Jo J, Filella X, Zanon G, Farrus B, Munoz M, Latre ML, Pahisa J, Velasco M, Fernandez P, Estape J, Ballesta AM.
Laboratory of Biochemistry (Unit for Cancer Research), Hospital Clinic, School of Medicine, Barcelona, Spain.
Anticancer Res 1999 Jul-Aug;19(4A):2551-5 Abstract quote
C-erbB-2, CEA and CA 15.3 serial serum determinations were performed in 250 patients (follow-up: 1-4 years, mean 2.5 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Ninety-five patients developed metastases during follow-up.
RESULTS: Abnormal c-erbB-2, CEA and CA 15.3 serum levels (> 20 U/ml, > 10 ng/ml or > 60 U/ml, respectively) prior to diagnosis were found in 28.4%, 31.6% and 46.3% of the 95 patients with recurrence, with a lead time of 4.2 +/- 2.4, 5.0 +/- 2.5 and 4.6 +/- 2.7 months, respectively. One of the tumor markers was the first sign of recurrence in 69.5% of the patients. Tumor marker specificity was 100% with levels lower than the cut-point in all 155 patients without recurrence. Tumor marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver or bone metastases. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (10/12, 83.3%) than in those without overexpression (1/34, 2.9%) (p = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PgR+ patients (CA 15.3) or in PgR- patients (C-erbB-2) (p < 0.015).
In conclusion, tumor markers are useful tools for the early diagnosis of metastases, being the first sign of recurrence in 69.5% of patients with relapse (76.3% in patients with metastases).
Preoperative values of CA 15-3 and CEA as prognostic factors in breast cancer: a multivariate analysis.
Canizares F, Sola J, Perez M, Tovar I, De Las Heras M, Salinas J, Penafiel R, Martinez P.
Department of Clinical Chemistry, University Hospital Virgen de la Arrixaca, Murcia, Spain.
Tumour Biol 2001 Sep-Oct;22(5):273-81 Abstract quote
The role of circulating tumor markers in providing prognostic information has not been widely studied. In the current study, serum levels of the carbohydrate antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) were determined preoperatively in 364 breast cancer patients with no clinical signs of metastasis.
The prognostic relevance of these markers for recurrence (175/364) and death of disease (104/175) was determined by Cox multivariate analysis, including the comparison with classical prognostic factors. High levels of both tumor markers were associated with aneuploid tumors with high S-phase fraction and high ornithine decarboxylase activity. CA 15-3 was highly associated with the number of positive lymph nodes and peritumoral lymphatic or blood vessel invasion. No significant associations were found between CEA or CA 15-3 levels and histologic grade, necrosis and steroid receptor status.
In univariate analysis, preoperative values, using optimum cutoff values of CA 15-3 (40 U/ml) and CEA (6 ng/ml), were statistically significant for relapse-free survival and overall survival.
In multivariate analysis, only node status, DNA ploidy and ornithine decarboxylase activity were independent predictors for relapse-free survival; the estrogen receptor status was a predictor of overall survival. In node-negative patients, ornithine decarboxylase activity was the only factor selected for relapse-free survival.
In node-positive patients, the number of lymph nodes and DNA ploidy were the only variables selected for relapse-free survival or overall survival. Estrogen receptor and ornithine decarboxylase activity were excluded for relapse-free survival, but were significant prognostic factors for overall survival.
INTERFERING DISEASES OR SUBSTANCES THAT ALTER LEVELS CHARACTERIZATION The effect of colonoscopy on tumor markers.
Scapa E, Broide E, Pinhasov I.
Institute of Gastroenterology, Liver Diseases, and Nutrition, Assaf Harofeh Medical Center, Zerifin, Israel.
Surg Laparosc Endosc 1997 Dec;7(6):477-9 Abstract quote
As preoperative elevated serum levels of carcinoembryonic antigen (CEA) and CA19.9 are markers for bad prognosis in colorectal cancer patients, it is important to decide whether preoperative total colonoscopy would make a significant change in their serum levels. CEA and CA 19.9 were evaluated in three groups of patients before and after colonoscopy.
The groups comprised the following: Group A, 20 patients with colorectal cancer; Group B, 17 patients with colorectal polyp of > or = 1-cm diameter; Group C, 16 patients with no colorectal pathology. CEA serum levels were found to be significantly lower after colonoscopy in all groups. CA19.9 was found to be significantly lower after colonoscopy only in Group B; it did not reach significance in Group A and was found not to be significantly higher in Group C.
A study of the effects of bowel preparation on CEA levels in patients undergoing surveillance colonoscopy.
So JB, Alexander DJ, Chia YW, Ngoi SS, Lee L, Goh PM.
Department of Surgery, National University Hospital, Singapore.
J R Coll Surg Edinb 1997 Apr;42(2):105-6 Abstract quote
Mechanical bowel preparation has been postulated to be another cause of "false rise' of serum carcinoembryonic antigen (CEA) levels. Furthermore, it was shown that high-risk patients for colorectal cancer had a greater rise in serum CEA after bowel preparation. To verify these findings, a prospective study of 24 consecutive patients in our surgical endoscopic unit on the effect of mechanical bowel preparation of serum CEA level as carried out from January to March 1994. Blood samples were taken before and after bowel preparation for patients undergoing surveillance colonoscopy for various reasons.
Our study did not show any relationship between serum CEA levels and bowel preparation. No rise of serum CEA was found even in high-risk patients after bowel preparation.
Tumor Marker Levels Elevate False-Positively in Postsurgical Breast Cancer Patients with High sGPT Levels or with Receiving Oral 5-FU or Its Derivatives.
Aaanuma K, Hama Y, Kobayashi S, Shingu K, Yokoyama S, Fujimori M, Kasuga Y, Amano J.
Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Breast Cancer 1999 Jul 25;6(3):181-186 Abstract quote
BACKGROUND: False elevation of tumor marker levels (TM) has been encountered in some postsurgical breast cancer patients.
METHODS: We investigated 33 postsurgical breast cancer patients whose TM (CEA, CA15-3, NCC-ST-439, or BCA225) measured every 3 months, showed elevation 3 times in a row in a 6-month period, and in whom metastases were not detected at theend of the 6-month period. Nine patients developed recurrence within 36 months of the end of the 6-month period and 24 patients did not develop recurrence for more than 36 months after the end of the 6-month period.
RESULTS: Seven patients who stopped treatment with oral 5-FU or its derivatives because of severe nausea and appetite loss did not develop recurrence. Normalization of TM (CEA, NCC-ST-439, or BCA225) manifested within 3 months of the interruption of the medication. Six patients who showed simultaneous increase in serum glutamic-pyruvic transaminase (sGPT) and TM (CEA or BCA225) in the initial 6months did not develop recurrence. Three of 6 patients did not take any anti-cancer drugs. Correlation coefficiencies of sGPT with CEA in 4 patients were 0.467, 0.569, 0.738, and 0.910 and those of sGPT with BCA225 in 3 patients were 0.663, 0.826, and 0.840.
CONCLUSION: A false-positive increase in CEA, NCC-ST-439 or BCA225 might be caused by treatment with oral 5-FU or its derivatives. CEA or BCA225 elevates false-positively in patients with high sGPT levels.
Clinical Diagnosis and Management by Laboratory Methods. 20th Edition. Henry JB. WB Saunders 2001.
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