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Licensed Unlicensed Requires Authentication Published by De Gruyter August 31, 2019

Evaluation of the usefulness of the simultaneous assay of fecal hemoglobin (Hb) and transferrin (Tf) in colorectal cancer screening – for the establishment of the Hb and Tf two-step cutoff assay (HTTC assay)

  • Ichiro Hirata EMAIL logo
From the journal Diagnosis



One of the issues of fecal immunochemical test (FIT) is false-negativity caused by hemoglobin degradation by bacteria. We investigated the usefulness of the transferrin assay, which is stable toward bacteria.


The study included 1174 patients who visited our hospital and underwent colonoscopy for some symptoms or for cancer screening. We compared the hemoglobin-transferrin combination assay with the hemoglobin-alone assay using the Discrete Clinical Chemistry Analyzer NS-Plus and 1174 clinical samples. In the combination assay, two hemoglobin cutoff values (a) and (b) and one transferrin cutoff value (c) were set. Cases with values of (a) or more were defined as primary positive and values lower than (b) were defined as negative. Cases with values between (a) and (b) underwent the transferrin assay. Then, cases with values of (c) or higher were defined as secondary positive. All primary and secondary positive cases were defined as positive. Among the combination of cutoff values (a), (b) and (c), we identified Method A exhibiting high specificity and a positive predictive value (PPV), and Method B exhibiting the highest sensitivity.


In Method A, the sensitivity of colorectal cancer detection increased from 67.3% to 68.2%, the specificity significantly (p = 0.0011) increased from 90.5% to 92.6%, and the PPV increased from 42.9% to 49.6% compared with the hemoglobin-alone assay. In Method B, the sensitivity increased significantly (p = 0.046) from 67.3% to 71.1% and the PPV increased from 42.9% to 44.8%.


This combination assay showed higher accuracy and effectiveness for colorectal cancer screening.

Corresponding author: Ichiro Hirata, MD, PhD, Department of Gastroenterology, National Federation of Health Insurance Societies Osaka Central Hospital, 3-3-30 Umeda, Kita-ku, Osaka 530-0001, Japan


The author thanks Ms. Hiroko Betsuyaku, Alfresa Pharma Corporation, for her support in this report.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


1. Saito H. Screening for colorectal cancer by immunochemical fecal occult blood testing. Jpn J Cancer Res 1996;87:1011–24.10.1111/j.1349-7006.1996.tb03103.xSearch in Google Scholar

2. Lee K-J, Inoue M, Otani T, Iwasaki M, Sasazuki S, Tsugane S. Colorectal cancer screening using fecal occult blood test and subsequent risk of colorectal cancer: a prospective cohort study in Japan. Cancer Detect Prev 2007;31:3–11.10.1016/j.cdp.2006.11.002Search in Google Scholar

3. Young GP, Symonds EL, Allison JE, Cole SR, Fraser CG, Halloran SP, et al. Advances in fecal occult blood tests: the FIT revolution. Dig Dis Sci 2015;60:609–22.10.1007/s10620-014-3445-3Search in Google Scholar

4. Schreuders EH, Ruco A, Rabeneck L, Schoen RE, Sung JJ, YoungGP, et al. Colorectal cancer screening: a global overview of existing programmes. Gut 2015;64:1637–49.10.1136/gutjnl-2014-309086Search in Google Scholar

5. Uchida K, Matsuse R, Toyoda K, Miyachi T, Okuda N, Tomita H. Fundamental study on immunological fecal occult blood test. J Clin Lab Inst Reag 1988;11:167–72.Search in Google Scholar

6. Kitagawa S, Miyagawa K, Ogawa M, Saito Y, Segawa K, Nagata Y, et al. The Japanese Society of Gastrointestinal Cancer Screening, 2006 Annual Report of Gastrointestinal Cancer Screening. J Gastroenterol Cancer Screening 2009;47:69–92.Search in Google Scholar

7. Uchida K, Matsuse R, Miyachi N, Okuda S, Tomita S, Miyoshi H, et al. Immunochemical detection of human blood in feces. Clin Chim Acta 1990;189:267–74.10.1016/0009-8981(90)90308-FSearch in Google Scholar

8. Hirata I, Yoshioka D, Shibata T, Nagasaka M, Takahama K, Matsuse R. 5. Early stage colorectal cancer screening 1) A fecal occult blood test – hemoglobin and transferrin simultaneous assay. I to Cho (Stomach and Intestine) 2010;45:725–33 [in Japanese].Search in Google Scholar

9. Senore C, Ederle A, Benazzato L, Arrigoni A, Silvani M, Fantin A, et al. Offering people a choice for colorectal cancer screening. Gut 2013;62:735–40.10.1136/gutjnl-2011-301013Search in Google Scholar PubMed

10. Randell E, Kennell M, Taher A, Antle S, Bursey F, Tavenor T, et al. Evaluation of Hemo Techt NS-Plus system for use in a province-wide colorectal cancer screening program. Clin Biochem 2013;46:365–8.10.1016/j.clinbiochem.2012.12.010Search in Google Scholar PubMed

11. Oono Y, Iriguchi Y, Doi Y, Tomino Y, Kishi D, Oda J, et al. A retrospective study of immunochemical fecal occult blood testing for colorectal cancer detection. Clin Chim Acta 2010;411:802–5.10.1016/j.cca.2010.02.057Search in Google Scholar PubMed

12. Group for “Study on appropriate procedures for cancer screening and establishment of evaluation method of the procedures” with 2004 Grant-in-aid for Cancer Research from Ministry of Health, Labor and Welfare. Guideline for colorectal cancer screening based on efficacy evaluation. Jpn J Cancer Chemother 2005;32;901–15.Search in Google Scholar

13. Yoshida Y. Primary and secondary prevention of colorectal cancer. J Jpn Soc Intern Med 1995;84;1380–7.10.2169/naika.84.1380Search in Google Scholar

Received: 2019-06-28
Accepted: 2019-08-08
Published Online: 2019-08-31
Published in Print: 2020-05-26

©2020 Walter de Gruyter GmbH, Berlin/Boston

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