High-Dose Hook Effect in a Grossly Elevated Tumour Marker: A Case Report of Delayed Diagnosis
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Keywords

Hook effect
Tumour marker
CA-125
Immunoassay interference
Delayed diagnosis

Abstract

The high-dose hook effect, in which a very high antigen concentration saturates both capture and detection antibodies in a
two-site immunometric assay and produces a falsely low or even normal result, is a well-described but infrequently encountered
analytical pitfall that can delay diagnosis when the falsely reassuring result does not match the clinical picture. We report a case
in which a patient with advanced ovarian carcinoma had a CA-125 result within the reference range despite a clinical
presentation strongly suggestive of advanced malignancy, delaying oncology referral by several weeks until an alert laboratory
scientist, noting the mismatch, requested sample dilution, which revealed a true CA-125 concentration exceeding the assay's
normal reportable range by more than one-hundred-fold. We describe the clinical and laboratory clues that should prompt
consideration of a hook effect, and recommend conditions under which routine dilution should be considered for clinically
discordant tumour marker results.

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References

Fernando SA, Wilson GS. "Studies of the "hook" effect in the one-step sandwich immunoassay". J Immunol Methods 151(1992): 47-66.

Tate J, Ward G. "Interferences in immunoassay". Clin Biochem Rev 25(2004): 105-120.

Cole LA, Rinne KM, Shahabi S, et al. "False-positive hCG assay results leading to unnecessary surgery and chemotherapy and needless occurrences of hCG-secreting tumors". Clin Chem 45(1999): 313-314.

Bolstad N, Warren DJ, Nustad K. "Heterophilic antibody interference in immunometric assays". Best Pract Res Clin Endocrinol Metab 27(2013): 647-661.

Sturgeon CM, Duffy MJ, Stenman UH, et al. "National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers". Clin Chem 54(2008): e11-e79.

Dodig S. "Interferences in quantitative immunochemical methods". Biochem Med 19(2009): 50-62.

Ismail AA, Walker PL, Barth JH, et al. "Wrong biochemistry results: two case reports and observational study in 5310 patients on potentially misleading thyroid-stimulating hormone and gonadotropin immunoassay results". Clin Chem 48(2002): 2023-2029.

Kricka LJ. "Human anti-animal antibody interferences in immunological assays". Clin Chem 45(1999): 942-956.

Marks V. "False-positive immunoassay results: a multicenter survey of erroneous immunoassay results from assays of 74 analytes in 10 donors from 66 laboratories in seven countries". Clin Chem 48(2002): 2008-2016.

Rulander NJ, Cardamone D, Senior M, et al. "Interference from heterophilic antibodies in a CA-125 assay after intraperitoneal antibody therapy". Arch Pathol Lab Med 137(2013): 1149-1151.

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