lmo Laboratory Medicine Online Lab Med Online ∗∗ 2093-6338 The Korean Society for Laboratory Medicine 10.3343/lmo.2019.9.3.146 lmo-9-146 Original Article False-positive Elevations in Carcinoembryonic Antigen Levels at a Health Screening Center ChungSoieM.D. Department of Laboratory Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea Corresponding author: Soie Chung, M.D. https://orcid.org/0000-0002-4528-1534 Department of Laboratory Medicine, Seoul National University Hospital Healthcare System Gangnam Center, 39th Fl. GFC, 152 Teheran-ro, Gangnam-gu, Seoul 06236, Korea Tel: +82-2-2112-5686, Fax: +82-2-2112-5794, E-mail: soiec@naver.com 07 2019 20 07 2019 9 3 146 152 19062018 20082018 21082018 Copyright © 2019 The Korean Society for Laboratory Medicine 2019 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background

Although routine screening of carcinoembryonic antigen (CEA) is not recommended for the early diagnosis of colorectal cancers, CEA levels are frequently measured in practice and during opportunistic health screening programs. We evaluated the frequency of false-positive results according to CEA level at a health screening center.

 Methods

The medical records of 25,786 participants who underwent a general health check-up and CEA testing at the Seoul National University Hospital Healthcare System Gangnam Center from March 2015 to February 2016 were reviewed. CEA levels were measured using the Architect i2000sr (Abbott Laboratories, USA). The cut-off level for elevated CEA was 5.0 ng/mL.

 Results

Among 25,786 participants who underwent CEA screening, 597 (2.3%) had CEA levels >5.0 ng/mL. Among 597 participants with elevated CEA levels, 12 (2.0%) had actual malignancies with CEA levels of 8.3–155.3 ng/mL. Diabetes, smoking, chronic obstructive pulmonary disease, and colonic polyps were considered as causes of false elevation. The false-positive rates of CEA according to level were as follows: 5.1–10.0 ng/mL, 99.5%; 10.1–15.0 ng/mL, 87.2%; 15.1–20.0 ng/mL, 100.0%; >20.0 ng/mL, 33.3%. A subsequent decrease in the CEA level after a 1-month follow-up was observed in 47.6% of all cases with elevated CEA levels.

 Conclusions

False elevation in CEA levels in the range of 5.0–20.0 ng/mL is common in patients who underwent testing at a health screening center. False-positive results above 20.0 ng/mL are less common. These data could provide a guide for the interpretation of elevated CEA level at a health screening center.

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Characteristics of the study population

Parameter All (N=25,786) CEA ≤5.0 (N=25,189) CEA >5.0 (N=597) P value∗
Age, yr (mean±SD) 56.7±8.7 51.0±11.4 57.4±10.7 0.189
Sex, N (%)        
Male 13,945 (54.1) 13,469 (53.5) 476 (79.7) <0.001
Female 11,841 (45.9) 11,720 (46.5) 121 (20.3)  
Smoking, N (%)
Current smoker 1,480 (5.7) 1,434 (5.7) 46 (7.7) 0.023
Non-smoker 24,306 (94.3) 23,755 (94.3) 551 (92.3)  
Diabetes, N (%) 1,740 (6.7) 1,646 (6.5) 94 (15.8) <0.001
COPD or inflammatory lesion in lung, N (%) 1,440 (5.6) 1,400 (5.4) 40 (6.6) <0.001
Colonic polyp, N (%) 4,420 (17.1) 4,163 (16.5) 257 (43.0) <0.001
BMI (kg/m2) 23.1 (21.0–25.2) 23.1 (21.0–25.2) 23.9 (21.9–25.7) 0.768
WBC (×103/µL) 5.4±1.5 5.4±1.5 6.3±1.9 <0.001
Hb, g/dL 14.4±1.5 14.4±1.5 15.0±1.4 0.041
Platelet (×103/µL) 228±52 228±52 221±52 0.536
HbA1c, % 5.7±0.6 5.7±0.6 6.0±1.0 <0.001
FBS, mg/dL 100±18 100±18 110±32 <0.001
Serum creatinine (mg/dL) 0.82±0.19 0.82±0.19 0.87±0.17 0.043
AST (IU/L) 24±12 24±12 27±15 <0.001
ALT (IU/L) 24±18 24±18 26±18 0.909
hs-CRP (mg/dL) 0.12±0.37 0.11±0.36 0.18±0.70 <0.001
FIT, N (%)†
Positive 164 (0.9) 155 (0.9) 9 (2.1) 0.019
Negative 17,239 (99.1) 16,826 (99.1) 413 (97.9)  
CEA, ng/mL 1.6 (1.1–2.3) 1.6 (1.1–2.2) 6.1 (5.4–7.3) <0.001

CEA ≤5.0 vs. CEA >5.0 ng/mL;

Values were presented as mean (SD), median (interquartile range), or number (percentage). Data were missing in 8,383 participants. Abbreviations: CEA, carcinoembryonic antigen; COPD, chronic obstructive pulmonary disease; BMI, body mass index; Hb, hemoglobin; HbA1c, glycated hemoglobin; FBS, fasting blood sugar; AST, aspartate aminotransferase; ALT, alanine aminotransferase; FIT, fecal immunochemical test; CEA, carcinoembryonic antigen; CA 19–9, cancer antigen 19–9.

Diagnosis of patients with elevated carcinoembryonic antigen levels

Diagnosis No. of participants (%) CEA (ng/mL)
Colorectal cancer 5 (0.8) 11.8 (9.8–17.0)
Lung cancer 4 (0.7) 16.9 (11.1–24.2)
Breast cancer 1 (0.2) N/A
Pancreatobiliary cancer 2 (0.3) N/A
Colonic polyp 223 (37.4) 6.0 (5.3–6.9)
Diabetes 38 (6.4) 6.3 (5.4–7.6)
Diabetes and colonic polyp 10 (1.7) 7.5 (5.8–11.5)
Diabetes and smoking 22 (3.7) 6.6 (5.7–8.5)
Diabetes, smoking, and colonic polyp 24 (4.0) 6.0 (5.3–6.7)
COPD or inflammatory lesion in the lung 40 (6.6) 5.7 (5.5–7.0)
No specific clinical condition 228∗ (38.2) 5.9 (5.3–7.4)
Total 597 (100.0) 6.1 (5.4–7.3)

The carcinoembryonic antigen level of 122 out of 228 participants (53.5%) normalized in a follow-up test.

CEA levels were presented as median (interquartile ranges). Abbreviations: CEA, carcinoembryonic antigen; COPD, chronic obstructive pulmonary disease; N/A, not applicable.

Case reviews for elevated carcinoembryonic antigen levels with malignancy

No. Sex Age CEA (ng/mL) Diagnosis FIT History of smoking
38062 M 54 21.8 Colorectal cancer, newly diagnosed Positive Ex-smoker
21494 M 86 9.9 Colorectal cancer, newly diagnosed Positive Non-smoker
8052 F 73 11.8 Colorectal cancer, newly diagnosed Positive Non-smoker
31435 M 65 12.1 Colorectal cancer, newly diagnosed Negative Ex-smoker
41541 M 77 25.5 Lung cancer, newly diagnosed N/A Current smoker
48991 M 65 10.3 Lung cancer, newly diagnosed N/A Non-smoker
13491 F 61 8.3 Breast cancer, newly diagnosed N/A Non-smoker
18613 M 77 155.3 Cholangiocarcinoma, newly diagnosed N/A Ex-smoker
10798 F 76 9.6 Colorectal cancer, on monitoring N/A Non-smoker
40687 M 45 13.5 Lung cancer, disease progression N/A Ex-smoker
27469 F 71 20.3 Lung cancer, disease progression N/A Non-smoker
35923 M 61 12.7 Pancreatic cancer, disease progression N/A Non-smoker

Abbreviations: CEA, carcinoembryonic antigen; FIT, fecal immunochemical test; N/A, not applicable.

False-positive rates of CEA according to level (N=597)

CEA level (ng/mL) Participants with proven malignancy, N Participants without evidence of malignancy, N∗ Subsequent decrease in the CEA level after follow-up, N† (%) False-positive rates (%)
5.1–10.0 (N=547) 3 544 275 (50.3) 99.5
10.1–15.0 (N=39) 5 34 8 (20.5) 87.2
15.1–20.0 (N=5) 0 5 1 (20.0)‡ 100.0
20.1–25.0 (N=3) 2 1§ 0 (0.0) 33.3
>25.0 (N=3) 2 1ll 0 (0.0) 33.3

No evidence of cancer on low-dose chest computed tomography (CT), abdomen CT, thyroid ultrasonography, colonoscopy, and esophagogastroduodenoscopy;

The percentage of decrease in the CEA level after follow-up according to each CEA level group

The initial and follow-up levels of CEA were 19.6 and 9.9 ng/mL, respectively;

The participant's CEA level was 20.8 ng/mL; llThe participant's CEA level was 30.4 ng/mL.

Abbreviation: CEA, carcinoembryonic antigen.