Elevated Preoperative Carcinoembryonic Antigen Levels Research Articles

Elevated levels of preoperative CA 15-3 and CEA serum levels have independently poor prognostic significance in breast cancer

BackgroundTo evaluate the prognostic value of preoperative tumor markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA), in breast cancers. Patients and methodsPreoperative CA 15-3 and CEA levels of 1681 patients were measured. The association of both tumor markers levels with clinicopathological parameters and outcomes was investigated by univariate and multivariate analyses. ResultsAmong 1681 patients, elevated preoperative CA15-3 and CEA levels were identified in 176 and 131 patients, respectively. Higher preoperative CA 15-3 and CEA levels were significantly associated with a larger tumor size, axillary node metastases, and advanced stage. Patients with elevated CA 15-3 and CEA levels showed worse survival, even in stage-matched analysis. Patients with normal levels of both CA15-3 and CEA showed better survival than those with one or both markers levels elevated. In multivariate analysis, elevated preoperative CA 15-3 and CEA levels were independent prognostic factors. The statistical significance of elevated preoperative tumor markers levels on survival was solidified with longer follow-up and larger study population. ConclusionsElevated preoperative CA 15-3 and CEA levels are associated with tumor burden and showed independent prognostic significance. Therefore, new treatment strategies are necessary for patients with elevated preoperative CA 15-3 and CEA levels in clinical practice.

Role of serum carcinoembryonic antigen in the detection of colorectal cancer before and after surgical resection

To determine whether serum levels of carcinoembryonic antigen (CEA) correlate with the presence of primary colorectal cancer (CRC), and/or recurrent CRC following radical resection. A total of 413 patients with CRC underwent radical surgery between January 1998 and December 2002 in our department and were enrolled in this study. The median follow-up period was 69 mo (range, 3-118 mo), and CRC recurrence was experienced by 90/413 (21.8%) patients. Serum levels of CEA were assayed preoperatively, and using a cutoff value of 5 ng/mL, patients were divided into two groups, those with normal serum CEA levels (e.g., ≤ 5 ng/mL) and those with elevated CEA levels (> 5 ng/mL). The overall sensitivity of CEA for the detection of primary CRC was 37.0%. The sensitivity of CEA according to stage, was 21.4%, 38.9%, and 41.7% for stages I-III, respectively. Moreover, for stage II and stage III cases, the 5-year disease-free survival rates were reduced for patients with elevated preoperative serum CEA levels (P < 0.05). The overall sensitivity of CEA for detecting recurrent CRC was 54.4%, and sensitivity rates of 36.6%, 66.7%, and 75.0% were associated with cases of local recurrence, single metastasis, and multiple metastases, respectively. In patients with normal serum levels of CEA preoperatively, the sensitivity of CEA for detecting recurrence was reduced compared with patients having a history of elevated CEA prior to radical resection (32.6% vs 77.3%, respectively, P < 0.05). CRC patients with normal serum CEA levels prior to resection maintained these levels during CRC recurrence, especially in cases of local recurrence vs cases of metastasis.

Clinicopathological study of p-T1aN0M0 non-small-cell lung cancer, as defined in the seventh edition of the TNM classification of malignant tumors

The seventh edition of the TNM Classification of Malignant Tumours was published in 2009. The present study was conducted to investigate the clinicopathological features of p-T1aN0M0 non-small-cell lung cancer, which is the earliest stage defined in the new tumor, node, metastasis (TNM) classification, in relation to patient prognosis. We retrospectively studied 162 patients, who underwent surgical resection at our institution for p-T1aN0M0 non-small-cell lung cancer, as re-categorized in the seventh TNM classification. Univariate and multivariate analyses of disease-free survival were performed. The mean tumor size was 13.2 ± 4.7 mm. The maximum tumor diameter was >10 mm in 104 cases (64.6%), and ≤ 10 mm in 58 (35.4%). The median follow-up period was 44.5 months. Univariate analysis showed that the 5-year disease-free survival rate of patients with and without preoperative serum carcinoembryonic antigen elevation was 50.8% and 95.1% (P<0.0001), respectively, that of patients with and without blood vessel or lymphatic invasion was 40.0% and 95.8% (positive vs negative, P<0.0001), respectively, and that of patients aged ≥ 70 years and <70 years was 86.8% and 96.1% (P=0.014), respectively. Multivariate analysis including these three clinicopathologic factors demonstrated that preoperative elevation of the carcinoembryonic antigen level and blood vessel or lymphatic invasion were independent prognostic factors. In patients with p-T1aN0M0 non-small-cell lung cancer, an elevated preoperative carcinoembryonic antigen level and blood vessel or lymphatic invasion tend to affect prognosis to a greater degree than tumor size. Therefore, the efficacy of adjuvant chemotherapy for these patients should be evaluated in clinical trials.

Persistently High Serum Carcinoembryonic Antigen Levels after Surgery Indicate Poor Prognosis in Patients with Stage I Non-Small-Cell Lung Cancer

The aim of this study is to evaluate the prognostic significance of preoperative and postoperative serum carcinoembryonic antigen (CEA) levels in patients with stage I non-small-cell lung cancer. A retrospective review of the medical records of 257 patients with stage I lung cancer undergoing surgical resection was performed. The clinical data of each patient was collected for analysis including age, smoking habits, gender, preoperative and postoperative serum CEA levels, tumor diameter, histologic type, visceral pleural invasion, pathologic stage, and type of operation. Adenocarcinoma was more often associated with elevated preoperative CEA level compared with non-adenocarcinoma. Tumor histology, however, did not influence postoperative CEA levels. In the univariate analysis, age, serum CEA level, and pathologic stage were prognostic factors. Patients with normal preoperative serum CEA levels had better 5-y survival than patients with high preoperative serum CEA levels (71.1% versus 54.6%, P = 0.016). The patients with a persistently high serum CEA level after surgery had worst prognosis. Multivariate analysis demonstrated that older age (≥65) and persistently high serum CEA levels were independent significant prognostic factors in patients with stage I lung cancer. Age (≥65 years) and preoperative and postoperative serum CEA levels are independent prognostic factors in patients with stage I lung cancer. Patients with a persistently high serum CEA level after surgery had worst survival, and may be good candidates for adjuvant chemotherapy.

A comparative study of protein expression in primary colorectal cancer and synchronous hepatic metastases: The significance of matrix metalloproteinase-1 expression as a predictor of liver metastasis

Objective. This study was undertaken to determine the ability of protein expression in primary colorectal cancer and metastatic liver tumour tissues to predict hepatic metastasis and intrahepatic recurrence. Material and methods. Sixty patients with colorectal cancer were enrolled in this study. The expression of the following five proteins was assessed by immunohistochemical (IHC) staining: carcinoembryonic antigen (CEA); vascular endothelial growth factor (VEGF); matrix metalloproteinase (MMP)-1; MMP-7; and tissue inhibitor of metalloproteinases (TIMP)-1. Protein expression was measured in patients with primary colorectal cancer without liver metastasis (Group A), in patients with primary colorectal cancer with liver metastasis (primary tumour; Group B), and in patients with resected metastatic liver tumour tissues (liver metastasis; Group C). Results. IHC staining revealed more protease activity (MMP-1 and -7) in Group B than in Group A. Angiogenic activity (positive VEGF expression) was significantly greater in Group C than in Group B. Multivariate analysis showed that positive MMP-1 expression, the presence of lymphovascular invasion, and an elevated pre-operative serum CEA level (> 5 ng/ml) were significantly related to synchronous liver metastasis. However, intrahepatic recurrence was not related to protein expression, the presence of lymphovascular invasion, or the pre-operative CEA level. Conclusions. Our findings suggest that protease activity is important for metastasis, and that angiogenic activity is essential for metastatic tumour growth. Furthermore, positive MMP-1 expression in primary colorectal tumour tissues was a significant predictor of liver metastasis. However, the prognostic impact of protein marker expression in terms of intrahepatic recurrence appears to be minimal.

Perioperative Carcinoembryonic Antigen Measurements to Predict Curability After Liver Resection for Colorectal Metastases

Perioperative carcinoembryonic antigen (CEA) blood level is a predictor of outcome after resection of colorectal liver metastases (CLMs). Prospective clinical study. Department of digestive surgery and transplantation. Between January 1, 2000, and December 31, 2004, CEA levels were routinely measured 1 week before and 6 weeks after CLM resection in 213 patients. The patients were divided into the following 3 groups: group A (n = 69) with normal preoperative and postoperative CEA levels, group B (n = 111) with elevated preoperative and normal postoperative CEA levels, and group C (n = 33) with elevated preoperative and postoperative CEA levels. The use of perioperative CEA levels to predict outcome after resection. The median survival was 45.4 months. The 5-year overall and disease-free survival rates were 50.2% and 21.9%, respectively, in group A, 38.5% and 18.3% in group B, and 0.0% and 0.0% in group C (P < .001). Univariate analysis showed that patients with elevated preoperative and postoperative CEA levels, multiple CLMs, large CLMs (> or =5 cm), advanced Fong clinical risk score, bilobar distribution, and hepatic pedicle lymph node involvement had significantly poorer overall and disease-free survival. By multivariate analysis, only perioperative CEA level, hepatic pedicle lymph node involvement, and number and size of CLMs were independent prognostic factors. The 5-year survival rates showed good correlation with perioperative CEA levels in all 3 patient groups. The predictive value of perioperative CEA levels is demonstrated. Carcinoembryonic antigen levels as early as 6 weeks after surgery may be helpful in assigning patients to adjuvant chemotherapy after resection of CLMs.

Preoperative Serum Carcinoembryonic Antigen Level as a Predictive Factor of Recurrence After Curative Resection of Colorectal Cancer

We evaluated the prognostic value of the preoperative serum carcinoembryonic antigen (CEA) level in patients with colorectal cancer (CRC). The study group comprised 638 patients. The optimal cutoff value for the preoperative serum CEA level was determined. Predictive factors of recurrence were evaluated using multivariate analyses. The relapse-free time was investigated according to the CEA level. All patients underwent potentially curative resection for CRC without distant metastasis, classified as stage I, II, or III. The optimal cutoff value for preoperative serum CEA level was 10 ng/ml. Elevated preoperative serum CEA level was observed in 92 patients. Multivariate analysis identified tumor-node-metastasis (TNM) stage and preoperative serum CEA level as independent predictive factors of recurrence. The relapse-free survival between CEA levels >10 ng/ml and <10 ng/ml significantly differed in patients with stage II and III. However, there was no significant difference in relapse-free survival between CEA levels >10 ng/ml and <10 ng/ml in patients with stage I. Preoperative serum CEA is a reliable predictive factor of recurrence after curative surgery in CRC patients and a useful indicator of the optimal treatment after resection, particularly for cases classified as stage II or stage III.

Prognostic value of carcinoembryonic antigen and CYFRA21-1 in patients with pathological stage I non-small cell lung cancer

The aim of this retrospective study was to assess the prognostic value of serum tumor markers (carcinoembryonic antigen (CEA) and CYFRA21-1) in patients with pathologic (p-) stage I non-small cell lung cancer (NSCLC) undergoing complete resection. Two hundred and seventy-five patients (163 males, 112 females, mean age 67.1 years) with p-stage I NSCLC who underwent complete resection at our institution between April 1999 and October 2004 were examined. Patients who had received preoperative chemotherapy or radiotherapy were excluded, as were patients who had multiple malignancies including multiple lung cancer. The serum levels of tumor markers were measured using commercially available immunoassays within 1 month before surgical resection. Serum levels of CEA and CYFRA21-1 higher than 5.0 and 2.8 ng/ml, respectively, were considered as positive according to the manufacture's instructions. The histological classification was adenocarcinoma in 193 patients, squamous cell carcinoma in 71, large cell carcinoma in 5, and other histological type in 6. One hundred and fifty-seven patients had T1 disease and 118 patients had T2 disease. The positive ratio of CEA and CYFRA21-1 was 25.7% and 13.7%, respectively, and in relation to histological type was 27.8% and 7.8% in adenocarcinoma, and 20.6% and 28.4% in squamous cell carcinoma. The overall 5-year survival rate was 79.3%. With a median follow-up of 35.5 month for surviving patients, those with initial CYFRA21-1 serum levels higher than 2.8 ng/ml had a significantly worse prognosis (p=0.0041). Patients with an elevated preoperative CEA level exceeding 5.0 ng/ml had a shorter disease-free survival period (p=0.0003). In patients with adenocarcinoma, a CEA level above 5.0 ng/ml was associated with shorter survival and early recurrence, whereas CYFRA21-1 showed no such association. In patients with squamous cell carcinoma, elevated preoperative CEA was not related to survival and recurrence. In these patients, preoperative CYFRA21-1 level exceeding 2.8 ng/ml was associated with a poorer outcome, whereas preoperative CYFRA21-1 level was not associated with cancer recurrence. The patients with p-stage I adenocarcinoma whose preoperative CEA level was high might be considered as good candidates for adjuvant chemotherapy. The prognostic value of CYFRA21-1 could not be confirmed for stage I NSCLC, and preoperative CYFRA21-1 level was not useful in selecting the candidates for adjuvant chemotherapy.

Large-cell carcinoma of the lung with a remarkable preoperative elevation of serum carcinoembryonic antigen level

Carcinoembryonic antigen, a serum tumor marker, is useful for diagnosing cancer and for following the response to therapy in cancer cases. Serum carcinoembryonic antigen levels are also important as a predictive tool in evaluating prognosis. A 56-year-old man presented with an abnormal shadow on a chest X-ray. His preoperative serum carcinoembryonic antigen was at an elevated level of 1274.0 ng/ml. Chest computed tomography revealed a tumor in the posterior segment of the right lung and a swollen right interlobar lymph node. Right lung pneumonectomy and node dissection were performed. A histological diagnosis determined that the tumor was a large-cell carcinoma at clinical stage IIA. Immunohistochemical analysis detected the production of carcinoembryonic antigen by the tumor cells. Following surgery, the patient's carcinoembryonic antigen levels were maintained within the normal range. This is a rare case of lung cancer with no evidence of recurrence and metastasis for 8 years despite markedly elevated preoperative carcinoembryonic antigen levels.

Invited commentary

The authors [1Hsu W.-H. Huang C.-S. Hsu H.-S. et al.Preoperative serum carcinoembryonic antigen level is a prognostic factor in women with early non-small-cell lung cancer.Ann Thorac Surg. 2007; 83: 419-424Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar] examined the role of serum carcinoembryonic antigen (CEA) level as a prognostic factor in patients with nonsmall cell lung cancer (NSCLC). Small studies have examined this serum marker; however CEA has not yet reached the level of evidence necessary for incorporation into consensus conference guidelines for staging or prognosis. Still, studies from Japan [2Inoue M. Minami M. Shiono H. Sawabata N. Ideguchi K. Okumura M. Clinicopathologic study of resected, peripheral, small-sized, non-small cell lung cancer tumors of 2 cm or less in diameter: pleural invasion and increase of serum carcinoembryonic antigen level as predictors of nodal involvement.J Thorac Cardiovasc Surg. 2006; 131: 988-993Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 3Sawabata N. Maeda H. Yokota S. et al.Postoperative serum carcinoembryonic antigen levels in patients with pathologic stage IA nonsmall cell lung carcinoma: subnormal levels as an indicator of favorable prognosis.Cancer. 2004; 101: 803-809Crossref PubMed Scopus (42) Google Scholar] and the current study from Taiwan, have suggested that increased levels of CEA may be associated with poorer prognosis. In this article, the authors describe a population of nonsmoking Taiwanese women (92.4% without a history of cigarette smoking) with predominantly adenocarcinoma and bronchoalveolar carcinoma (83.4%). Lobectomy was performed in 87% of these individuals. Elevated preoperative CEA levels (>6.0 ng/mL) and larger tumor size were associated with poorer prognosis. Are these findings related to histology, ethnicity, or other genetic alterations that may predispose to adenocarcinoma in nonsmoking women? The answer to these and other questions will require a larger analysis of prospectively collected serum, tissue, and clinical data. However, until completion of these analyses, patients with an adenocarcinoma of the lung, particularly in women nonsmokers, may be considered for serum CEA level determination. Patients with CEA ≥6 ng/mL may represent a population with poorer survival mandating closer follow-up and consideration for multimodality or other targeted therapies [4Okamoto T. Nakamura T. Ikeda J. et al.Serum carcinoembryonic antigen as a predictive marker for sensitivity to gefitinib in advanced non-small cell lung cancer.Eur J Cancer. 2005; 41: 1286-1290Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar]. Although adjuvant chemotherapy is not a current recommendation for stage I NSCLC, the ability to predict those stage I patients with poor prognosis would be helpful. Early-stage, poor-prognosis patients could be selected for specific therapies for subsequent survival benefit compared with current models of observation alone. The poorer survival with increased preoperative CEA in nonsmoking Asian women must be considered in relationship to women (and men) of various ethnicities and smoking status. These small retrospective independent studies, may provide models for subsequent evaluation of CEA and other serum markers for staging, prognosis, and therapy for patients with early stage NSCLC. Preoperative Serum Carcinoembryonic Antigen Level is a Prognostic Factor in Women With Early Non–Small-Cell Lung CancerThe Annals of Thoracic SurgeryVol. 83Issue 2PreviewCarcinoembryonic antigen (CEA) is one of the markers evaluated in patients with non–small cell lung cancer (NSCLC). The significance of the preoperative serum CEA level in female patients with NSCLC is seldom discussed. In this study, we conducted a retrospective review to investigate the prognostic significance of the preoperative CEA level in female patients with stage I NSCLC. Full-Text PDF

Pre-operative carcino-embryonic antigen and survival in patients with colorectal cancer.

The relationship between pre-operative levels of carcino-embryonic antigen (CEA), resectability of the primary tumour, the extent of tumour spread and subsequent survival was studied in 333 patients with colorectal cancer. Twenty-five per cent of patients undergoing 'curative' resection had elevated CEA levels compared with fifty-six per cent of patients receiving palliative treatment. Twenty-five per cent of patients with Dukes B or C tumours had elevated pre-operative CEA levels compared with seventy per cent of patients with stage D disease. In patients undergoing 'curative' resection there was no correlation between pre-operative CEA levels and subsequent survival. In patients undergoing palliative resection, elevated pre-operative CEA levels were associated with poor survival. Although pre-operative levels of CEA reflect the extent of the underlying disease process, estimations of pre-operative CEA levels are of limited value in predicting patients with a poor prognosis following curative resection for colorectal carcinoma.

Invited commentary

Since the early 1970s, several studies have shown that high carcinoembryonic antigen (CEA) levels were a potential marker of poor prognosis in nonsmall cell lung cancer (NSCLC). Abnormally elevated CEA levels were reported in 30% to 70% of patients with NSCLC and were most frequently observed in patients with adenocarcinoma and advanced stage carcinoma. Despite its potential value, CEA was often falsely elevated in smokers and in patients with restrictive or obstructive pulmonary disease. Consequently, the stage of disease and performance status of the patients remained better predictors of survival than CEA, and in 1997, The American Thoracic Society and the European Respiratory Society did not recommend the routine measurement of CEA for patients with NSCLC, because it did not influence the management of these patients. However, the past decade has been associated with significant changes in the mode of presentation and treatment of NSCLCs. Adenocarcinoma has become more frequent than squamous cell carcinoma in North America and Asia, low-dose chest computed tomography has been popularized, the incidence of bronchioloalveolar carcinoma has been rising (particularly in nonsmokers), and chemotherapy has been proven beneficial in patients with early stage NSCLC. These changes have brought a whole new set of questions in our current management of patients with stage IA and IB NSCLC. Do all patients with very early stage NSCLC require a lobectomy or would segmentectomy be an appropriate operation in some patients? Do all bronchioloalveolar carcinomas have to be treated similarly to other NSCLCs, or is there a spectrum of disease between bronchioloalveolar carcinoma and adenocarcinoma? Do all patients with early stage NSCLC require chemotherapy in addition to surgery, and should they receive it before or after surgery? Refinements to our current evaluation of patients with early stage NSCLC is needed to answer some of these questions. The measurement of tumor markers could potentially be part of this evaluation. Carcinoembryonic antigen is an inexpensive and readily available serum marker that has been shown to be one of the few independent preoperative predictors of survival in patients with small adenocarcinoma. High preoperative CEA level has also been shown to be associated with a higher risk of nodal metastasis in patients with NSCLC, and particularly in patients with clinical stage IA adenocarcinoma. The combination of a normal preoperative CEA level with a high tumor disappearance rate, which is determined by the ratio of the tumor area between the mediastinal and the lung windows on chest computed tomography, was recently shown to preoperatively predict the selection of a group of patients with peripheral adenocarcinoma that had no nodal metastasis [1Takamochi K, Nagai K, Yoshida J, et al. Pathologic N0 status in pulmonary adenocarcinoma is predictable by combining serum carcinoembryonic antigen level and computed tomographic findings? J Thorac Cardiovasc Surg 2001;122:325–30.Google Scholar]. This study from Okada and colleagues looking at the role of histology and smoking status on the prognostic value of CEA in patients with clinical stage I NSCLC reiterates the importance of CEA as an independent preoperative prognostic variable along with age, gender, and size of the tumor [2Okada M, Nishio W, Sakamoto T, et al. Effect of histologic type and smoking status on interpretation of serum carcinoembryonic antigen value in non–small cell lung carcinoma. Ann Thorac Surg 2004;78:1004–10.Google Scholar]. The authors eventually demonstrate that elevated preoperative CEA level had a predictive impact on prognosis only in nonsmokers with adenocarcinoma; this group also included previous smokers that had stopped smoking before their diagnosis of NSCLC. This finding may explain some of the discrepancies that were observed in the past and the low accuracy of elevated CEA level to predict outcome when it is indifferently applied to all patients with NSCLC. The importance of postoperative CEA level on outcome in patients with adenocarcinoma or squamous cell carcinoma and pathologically proven stage I disease is also briefly reported in the study. Unfortunately, the authors did not directly compare the outcome of patients that normalized their CEA level postoperatively to those that did not. However, the persistence of elevated CEA level despite apparently complete surgical resection is likely an important finding that is related to the persistence of undetected micrometastasis in mediastinal lymph nodes or elsewhere in the body. Hence, this group of patients is certainly at high risk of recurrence and could potentially benefit most from aggressive adjuvant chemotherapy. In conclusion, CEA is a tumor marker that may help to stratify patients with early stage NSCLC. The prognostic potential appears to be valid, mainly in nonsmokers or previous smokers, and it seems to be particularly useful in patients with adenocarcinoma. As the treatment of patients with early stage NSCLC is being refined in prospective studies, preoperative and postoperative CEA level appear to be an important factor to consider.

Time-dependency of the prognostic effect of carcinoembryonic antigen and p53 protein in colorectal adenocarcinoma.

This study examined the prognostic information regarding the risk of postoperative tumor recurrence obtained by simultaneous determination of preoperative serum carcinoembryonic antigen (CEA) and immunohistochemical expression of p53 protein in tumor tissue from patients with colorectal carcinoma. A retrospective study of 174 patients (AJCC/UICC Stages I, II and III) was conducted. Serum CEA levels were determined by an enzyme-linked immunoadsorbent assay. Immunohistochemical expression of nuclear p53 protein was assessed in formalin fixed, paraffin embedded archival tumor tissue. The results of both factors were categorized by clinical and histopathologic variables. The relative prognostic significance of all factors with regard to disease free survival was assessed by Cox proportional hazards regression analysis. The stability of the predictive value of both markers was assessed: 1) by splitting the follow-up into three intervals and performing separate analyses for each period and 2) graphically by plotting the corresponding cumulative hazards ratio along the follow-up. Eighty-two (47%) tumors manifested overexpression of p53 protein and 60 tumors (34.4%) exhibited elevated serum CEA levels (cutoff value of 5 ng/mL). p53 positive immunostaining and elevated CEA levels were associated with low cumulative disease free survival at 60 months' of follow-up, and proved to have independent prognostic significance. Analysis performed in different time periods of follow-up showed that the prognostic effect of both markers was not stable over time. The predictive significance of CEA and p53 changed along the study periods. An elevated preoperative CEA level was an indicator of a high risk of recurrence only during the first 2 years after surgery (hazards ratio, 3.26; 95% confidence interval 95% CI, 1.65-6.42). The presence of p53 immunoreactivity in the primary tumor was an indicator of a high risk of recurrence only after the first year of follow-up (hazards ratio, 4.02; 95% CI, 1.68-9.6). The serum CEA level and expression of p53 protein provide complementary prognostic information. Time-dependency of the prognostic influence of both parameters should be taken into consideration when establishing postoperative predictive estimations.

Time-dependency of the prognostic effect of carcinoembryonic antigen and p53 protein in colorectal adenocarcinoma

BACKGROUND This study examined the prognostic information regarding the risk of postoperative tumor recurrence obtained by simultaneous determination of preoperative serum carcinoembryonic antigen (CEA) and immunohistochemical expression of p53 protein in tumor tissue from patients with colorectal carcinoma. METHODS A retrospective study of 174 patients (AJCC/UICC Stages I, II and III) was conducted. Serum CEA levels were determined by an enzyme-linked immunoadsorbent assay. Immunohistochemical expression of nuclear p53 protein was assessed in formalin fixed, paraffin embedded archival tumor tissue. The results of both factors were categorized by clinical and histopathologic variables. The relative prognostic significance of all factors with regard to disease free survival was assessed by Cox proportional hazards regression analysis. The stability of the predictive value of both markers was assessed: 1) by splitting the follow-up into three intervals and performing separate analyses for each period and 2) graphically by plotting the corresponding cumulative hazards ratio along the follow-up. RESULTS Eighty-two (47%) tumors manifested overexpression of p53 protein and 60 tumors (34.4%) exhibited elevated serum CEA levels (cutoff value of 5 ng/mL). p53 positive immunostaing and elevated CEA levels were associated with low cumulative disease free survival at 60 months' of follow-up, and proved to have independent prognostic significance. Analysis performed in different time periods of follow-up showed that the prognostic effect of both markers was not stable over time. The predictive significance of CEA and p53 changed along the study periods. An elevated preoperative CEA level was an indicator of a high risk of recurrence only during the first 2 years after surgery (hazards ratio, 3.26; 95% confidence interval [95% CI], 1.65–6.42). The presence of p53 immunoreactivity in the primary tumor was an indicator of a high risk of recurrence only after the first year of follow-up (hazards ratio, 4.02; 95% CI, 1.68–9.6). CONCLUSIONS The serum CEA level and expression of p53 protein provide complementary prognostic information. Time-dependency of the prognostic influence of both parameters should be taken into consideration when establishing postoperative predictive estimations. Cancer 2000;88:35–41. © 2000 American Cancer Society.

CEA levels in head and neck cancer.

Serum carcinoembryonic antigen (CEA) levels were determined for 439 patients with squamous carcinoma of the head and neck region, 154 healthy smokers, and 122 nonsmokers. Among nonsmokers 95% of the CEA levels did not exceed 5 ng/ml, but among smokers this discriminatory level was 7 ng/ml. Among tumor-bearing patients 36% of the CEA levels exceeded 5 ng/ml but only 17% exceeded 7 ng/ml. Both the incidence and magnitude of CEA elevations correlated with clinical stage of tumor; however, excluding patients with clinically apparent advanced malignancies, the incidence and magnitude of elevations were similar among tumor-bearing patients, tumor-free treated patients, and smokers. Although not predictive of ultimate survival, elevated preoperative CEA levels declined to the range of normals after resection. Similarly, during palliative irradiation for incurable tumors, CEA levels declined with regression of tumor. Irradiation did not nonspecifically elevate CEA levels. The data indicate that in patients with head and neck squamous carcinomas CEA level is not likely to contribute to a determination of prognosis after therapy; however, serial determinations may have adjunctive value in monitoring tumor response.