B-320 Understanding CA 72-4: Exploring False Positives in Clinical Context

Abstract Background CA 72-4, initially identified in 1981 as an antigen reactive to murine antibodies, is a glycoprotein expressed on the cell surface of certain carcinoma cells. Its production is elevated in various cancers, including ovarian, pancreatic, colorectal, and gastric cancer. However, CA 72-4 serum concentration may rise in non-cancerous conditions, leading to potential misdiagnosis and a low positive predictive value (PPV), particularly in asymptomatic patients. Our aim in this study was to describe CA 72-4 false positive values and assess the pathological conditions and pharmacological treatments associated with this. We also intended to compare other tumour markers status in false and true positive results of CA 72-4. Methods A retrospective analysis form pseudo-anonymized database was conducted using data from 1290 laboratory analysis from different patients taking a blood test at our laboratory hospital from 2017 to 2019. CA 72-4 and other tumour markers were analysed by ECLIA (Roche Diagnostics Gmbh. Mannheim, Germany). Results Among 1290 CA 72-4 laboratory tests in different patients, 204 were considered positive because they were above the reference interval (<7 U/mL). Within this subgroup, 44 of the 204 were clearly classified as false positives, as patients were not diagnosed with any form of neoplastic process. 45% of cases were between 7-14 U/mL (group 1), 30% were between 14-28 U/mL (group 2), and finally 25% of patients were above 28 U/mL ranging from 35.1 to 240.4 U/mL (group 3). Interestingly, CA19-9, CA 125 and CEA were measured in 37 of the false positive cases and it was found that 59.5% had at least another tumour marker above the reference range. In 103 true positive cases it was found that 88% of patients had at least one tumour marker above the normal range. Patients exhibiting false positive results for CA 72-4 demonstrated a wide spectrum of pathological conditions, with pulmonary disease, inflammation, infection, and heart and kidney disease emerging as the most prevalent. Group 1 patients most common underlying pathologies were pulmonary disease in 25%, heart disease in 25% and either viral or bacterial infection in 60% of patients. Group 2 patients most common pathologies were heart disease in 42%, pulmonary disease in 33% and infection in 25% of patients. In group 3 patients, renal disease was present in 45% of patients, heart disease was found in 45% of patients and inflammation/sepsis was found in 36% of patients. When looking into pharmacological treatment, 86.3% of patients were taking at least one of previously described treatments increasing CA 72-4 in serum; proton pump inhibitors, corticosteroids, antiplatelet drugs and colchicine. Drug treatment proportion was very similar across the different groups. Conclusions CA72-4 false positive cases are sometimes in conjunction with other false positive tumour markers but not in the same proportion as true positives. In addition, most false positive patients can be explained by pharmacological treatments. This research may help in the understanding and identification of potential factors influencing tumor marker levels and thus contribute to the interpretation of results.