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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 26  |  Issue : 2  |  Page : 175-179

Variation of serum carcinoembryonic antigen with grading and radiological staging in colorectal malignancy


Department of General Surgery, Government Medical College, Kozhikode, Kerala, India

Date of Submission29-Jul-2020
Date of Decision04-Aug-2020
Date of Acceptance13-Aug-2020
Date of Web Publication07-Nov-2020

Correspondence Address:
Dr. Akshaya Mohan
Department of General Surgery, Government Medical College, Kozhikode, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ksj.ksj_6_20

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  Abstract 


Introduction: Serum carcinoembryonic antigen (CEA) is used universally as a tumour marker for colorectal malignancies. The study aims to compare the serum CEA levels in different histopathological grades and radiological stages and to see if there is a relation between them so that advanced stage can be predicted early with serum CEA level. Methodology: An observational study was done on 101 patients with colorectal malignancies. Pre-operative serum CEA value, radiological staging and pathological grading were compared. Results: Fifty-eight patients were male and 43 female. The mean age was 62.6 years. The mean serum CEA value was 14.99 ng/ml. There was a significant relation between CEA and T staging. There was no significant relation with nodal status or metastases or grading. Conclusion: The study revealed a relationship of higher T staging with CEA. No relationship was found with nodal/metastasis status/grading. We can suspect tumours with advanced T stage clinically, if CEA is elevated in patients with colorectal malignancies.

Keywords: Carcinoembryonic antigen, colorectal malignancies, histopathological grade radiological stage


How to cite this article:
Mohan A, Rajesh M R, Sreejayan M P. Variation of serum carcinoembryonic antigen with grading and radiological staging in colorectal malignancy. Kerala Surg J 2020;26:175-9

How to cite this URL:
Mohan A, Rajesh M R, Sreejayan M P. Variation of serum carcinoembryonic antigen with grading and radiological staging in colorectal malignancy. Kerala Surg J [serial online] 2020 [cited 2020 Dec 2];26:175-9. Available from: http://www.keralasurgj.com/text.asp?2020/26/2/175/300244




  Introduction Top


Colorectal malignancies are increasing in number compared to older times. We use imaging, histopathology and tumour markers to diagnose, stage and follow up patients with carcinoma colon. Serum carcinoembryonic antigen (CEA) is used as a tumour marker universally for colorectal malignancies. The goal of the present study was to see if this tumour marker can be used to predict the severity of the disease in terms of staging and grading and if advanced diseases can be identified early with CEA.


  Methodology Top


The study aimed to study the relationship between pre-operative serum CEA levels and histological grading of colorectal malignancies and to find if there is any relation between pre-operative serum CEA levels and radiological staging of colorectal malignancies. An observational study was conducted in the Department of General Surgery, Calicut Medical College, on patients with colorectal malignancy from February 2018 to August 2019 and who underwent surgery. All patients with colorectal malignancy whose pre-operative serum CEA and contrast-enhanced computed tomography (CECT) abdomen were done were included. Patients whose pre-operative serum CEA and CECT abdomen were not done were excluded. The variables pre-operative serum CEA value, histological grading and radiological staging of colorectal malignancy were considered.


  Results Top


In the 101 patients, the mean age was 62.6 years (range, 28–87 years). Majority of the patients were observed in the range of 61–90 years [Figure 1]. Male: female ratio was 58:43. The pre-operative serum CEA value ranged from 0.1 to 216 ng/ml, with a mean CEA of 14.99 ng/ml. Fifty-five patients had CEA values ≤5 ng/ml and 46 had more. Tumour, node and metastasis (TNM) staging showed that majority of the patients were in Stage 3 (78). T3 lesions and N1 nodes were most common [Figure 2]. There was a significant relation between CEA and T stage but no relation with node, metastasis status or stage grouping. Assessing of the CEA values in the different TNM stages of carcinoma of the colon, it was seen that amongst the 101 patients, there was no patient with T1 lesion. Of 33 patients with T2 lesion, 24 had normal CEA and 9 had high value. Amongst the 51 patients in T3 stage, 22 had normal CEA and 29 had high value. In this stage, the high value of CEA appeared to be more in larger number of patients, however, the difference in mean values was not statistically significant. Of 17 patients with T4 lesion, 9 had normal CEA and 8 had high value. The Chi-square test did not show any statistical significance of difference [Figure 3]. Amongst 21 patients studied with N0 lesion, 16 had normal CEA and 5 had high value. Of the 51 patients with N1 lesion, 25 had normal value and 26 had high value. Of the 29 patients N2 lesion, 14 had normal value and 15 had high value. The Chi-square test showed that there was no statistically significant variation amongst the patients with various node statuses [Figure 4]. A study of the metastatic level showed that 97 had no metastasis. Amongst them, 53 had normal CEA and 44 had high value. Amongst the four patients with distant metastasis, two had normal value and two had elevated CEA. There was no statistically significant difference [Figure 5]. Considering the stage grouping, the maximum number of patients was seen in the Stage 3 level, and in them, of the total of 78, 40 had high CEA level against 38 who had normal CEA level. This difference was not statistically significant. In Stage 1, Stage 2 and Stage 4, more patients had normal CEA than elevated levels [Figure 6]. The grading of the tumours showed that 83 were well differentiated, 12 moderately differentiated and 6 poorly differentiated. Of the 83 patients with well-differentiated carcinoma, 45 had normal CEA values and 38 had > 5 ng/ml. Of the 12 patients with moderately differentiated cancer, 8 had normal CEA and 4 had high CEA. Amongst the six patients with poorly differentiated malignancy, two had normal and four had high CEA. The Chi-square test showed that the differences were not statistically significant relation between CEA and various grades of cancer [Figure 7].
Figure 1: Age frequency distribution in the study

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Figure 2: Stage distribution of patients

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Figure 3: T stage versus carcinoembryonic antigen comparison

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Figure 4: N stage and carcinoembryonic antigen comparison

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Figure 5: M stage and carcinoembryonic antigen comparison

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Figure 6: Stage grouping versus carcinoembryonic antigen comparison

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Figure 7: Grading versus carcinoembryonic antigen comparison

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  Discussion Top


Different values obtained from the analysis were compared with those reported in the literature [Table 1]. As per Huang et al.,[1] patients with high (>5.0 ng/mL) pre-chemoradiotherapy (CRT) CEA concentrations were likely to have more advanced clinical T stage than those with normal (5.0 ng/mL) pre-CRT CEA.
Table 1: Comparison of similar studies

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As per Riaz et al.,[2] pre-operative CEA levels were associated with age, BMI, American Society of Anaesthesiologists score and tumour stage. Tumour characteristics associated with higher CEA levels were higher AJCC stage, signet cell subtype and both undifferentiated and poorly differentiated tumours. Barone et al.[3] demonstrated a correlation of CEA with performance status and with metastatic pattern. Fletcher [4] reviewed the sensitivity and specificity of CEA levels and found that sensitivity decreased while the specificity increased for higher CEA cut-off points (5 ng and 10 ng). Vukobrat-Bijedic et al.[5] found that well-differentiated adenocarcinoma is accompanied by higher CEA serum concentration.

Ochiai et al.[6] did not find significantly higher CEA and CA19-9 levels in patients who had recorded metastases into lymph nodes. As per the study by the American Society of Clinical Oncology,[7] serum CEA was elevated in 50% of the patients with tumour extension to the lymph nodes and in 75% of the patients with distant metastasis. Elevated serum CEA predicted a more advanced stage in earlier reports.[8]

Bhatnagar et al.[9] showed that more CEA per gram of total protein was produced by well-differentiated colorectal cancers than by poorly differentiated specimens. Serum CEA has also been reported to trend higher in patients with well-differentiated tumours than in those with poorly differentiated tumours in a study by Goslin et al.[10] Duffy [11] suggested that a lack of differentiation or poor differentiation may explain why some patients with advanced colorectal cancer do not show increased serum concentrations of CEA. Rognum [12] have shown lower serum CEA in patients with tumours having a near diploid pattern. Levy et al.[13] also stated that CEA and CA19-9 are statistically significantly different in early and metastatic colorectal cancer. CEA might play a role in the metastatic process.[14] The role of CEA in cancer dissemination was revealed by Hostetter et al.[15]

Priolli et al.[16] found an association between increased CEA and loss of histological differentiation. Advanced-staged neoplasia exhibits increased CEA.[17] Hamada et al.[18] also showed that well-differentiated tumours had low CEA in the blood. Wang et al.[19] found well-differentiated tumours to have low levels of CEA in the blood. The exact pre-operative serum CEA value did not correlate with tumour grade in the study by Zeng et al.[20] Midiri et al.[21] found low concentration in early stage but no significant correlations with cancer grading. Thus, comparing our study, most of the previous reports suggest a relation between the advanced stage and CEA. However, relation with grading varied with the different studies.


  Conclusion Top


The present study revealed a relationship with higher T staging with CEA in patients with colorectal malignancies. Most of the previous studies supported this finding. No relation was found with nodal/metastasis status/grading. We can suspect tumours with advanced T stage clinically, if CEA is elevated in patients with colorectal malignancies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Huang CS, Lin JK, Wang LW, Liang WY, Lin CC, Lan YT, et al. Assessment of the value of carcinoembryonic antigen reduction ratio as a prognosis factor in rectal cancer. Am J Surg. 2014;208:99-105. doi: 10.1016/j.amjsurg.2013.08.054. Epub 2014 Jan 16. PMID: 24524862.  Back to cited text no. 1
    
2.
Riaz A, Wilkins S, Staples M, Hin C, Lee A, Oliva K, et al. The role of preoperative CEA in the management of colorectal cancer: A cohort study from two cancer centres. Int J Surg 2019;64:10-5.  Back to cited text no. 2
    
3.
Barone C, Astone A, Cassano A, Garufi C, Astone P, Grieco A, et al. Advanced colon cancer: Staging and prognosis by CEA test. Oncology 1990;47:128-32.  Back to cited text no. 3
    
4.
Fletcher RH. Carcinoembryonic antigen. Ann Intern Med 1986;104:66-73.  Back to cited text no. 4
    
5.
Vukobrat-Bijedic Z, Husic-Selimovic A, Sofic A, Bijedic N, Bjelogrlic I, Gogov B, et al. Cancer antigens (CEA and CA 19-9) as markers of advanced stage of colorectal carcinoma. Med Arch (Sarajevo, Bosnia Herzegovina) 2013;67:397-401.  Back to cited text no. 5
    
6.
Ochiai H, Ohishi T, Osumi K, Tokuyama J, Urakami H, Seki S, et al. Reevaluation of serum p53 antibody as a tumor marker in colorectal cancer patients. Surg Today 2012;42:164-8.  Back to cited text no. 6
    
7.
Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. Adopted on May 17, 1996 by the American Society of Clinical Oncology. J Clin Oncol 1996;14:2843-77.  Back to cited text no. 7
    
8.
Kirat HT, Ozturk E, Lavery IC, Kiran RP. The predictive value of preoperative carcinoembryonic antigen level in the prognosis of colon cancer. Am J Surg 2012;204:447-52.  Back to cited text no. 8
    
9.
Bhatnagar J, Tewari HB, Bhatnagar M, Austin GE. Comparison of carcinoembryonic antigen in tissue and serum with grade and stage of colon cancer. Anticancer Res 1999;19:2181-7.  Back to cited text no. 9
    
10.
Goslin R, O'Brien MJ, Steele G, Mayer R, Wilson R, Corson JM, et al. Correlation of plasma CEA and CEA tissue staining in poorly differentiated colorectal cancer. Am J Med 1981;71:246-53.  Back to cited text no. 10
    
11.
Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: Is it clinically useful? Clin Chem 2001;47:624-30.  Back to cited text no. 11
    
12.
Rognum TO. New approach in carcinoembryonic antigen-guided follow-up of large-bowel carcinoma patients. Scand J Gastroenterol 1986;21:641-9.  Back to cited text no. 12
    
13.
Levy M, Visokai V, Lipska L, Topolcan O. Tumor markers in staging and prognosis of colorectal carcinoma. Neoplasma 2008;55:138-42.  Back to cited text no. 13
    
14.
Hammarström S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol 1999;9:67-81.  Back to cited text no. 14
    
15.
Hostetter RB, Augustus LB, Mankarious R, Chi KF, Fan D, Toth C, et al. Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. Natl Cancer Inst 1990;82:380-5.  Back to cited text no. 15
    
16.
Priolli DG, Martinez CA, Piovesan H, Cardinalli IA, Margarido NF, Waisberg J. Morphofunctional malignancy grading is a valuable prognostic factor for colorectal cancer. Arq Gastroenterol 2010;47:225-32.  Back to cited text no. 16
    
17.
Nathanson SD, Schultz L, Tilley B, Kambouris A. Carcinomas of the colon and rectum. A comparison of staging classifications. Am Surg 1986;52:428-33.  Back to cited text no. 17
    
18.
Hamada Y, Yamamura M, Hioki K, Yamamoto M, Nagura H, Watanabe K. Immunohistochemical study of carcinoembryonic antigen in patients with colorectal cancer. Correlation with plasma carcinoembryonic antigen levels. Cancer 1985;55:136-41.  Back to cited text no. 18
    
19.
Wang JY, Tang R, Chiang JM. Value of carcinoembryonic antigen in the management of colorectal cancer. Dis Colon Rectum 1994;37:272-7.  Back to cited text no. 19
    
20.
Zeng Z, Cohen AM, Urmacher C. Usefulness of carcinoembryonic antigen monitoring despite normal preoperative values in node-positive colon cancer patients. Dis Colon Rectum 1993;36:1063-8.  Back to cited text no. 20
    
21.
Midiri C, Amanti C, Consorti F, Benedetti M, Del BS, Di TU, et al. Usefulness of preoperative CEA levels in the assessment of colorectal cancer patient stage. J Surg Oncol 1983;22:257-60.  Back to cited text no. 21
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
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