Pre-analytical stability of the CEA, CYFRA 21.1, NSE, CA125 and HE4 tumor markers.

Background: For lung cancer, circulating tumor markers (TM) are available to guide clinical treatment decisions. To ensure adequate accuracy, pre-analytical instabilities need to be known and addressed in the pre-analytical laboratory protocols.

Objective: This study investigates the pre-analytical stability of CA125, CEA, CYFRA 21.1, HE4 and NSE for the following pre-analytical variables and procedures; i) whole blood stability, ii) serum freeze-thaw cycles, iii) electric vibration mixing and iv) serum storage at different temperatures.

Methods: Left-over patient samples were used and for every investigated variable six patient samples were used and analysed in duplicate. Acceptance criteria were based on analytical performance specifications based on biological variation and significant differences with baseline.

Results: Whole blood was stable for at least 6 hours for all TM except for NSE. Two freeze-thaw cycles were acceptable for all TM except CYFRA 21.1. Electric vibration mixing was allowed for all TM except for CYFRA 21.1. Serum stability at 4°C was 7 days for CEA, CA125, CYFRA 21.1 and HE4 and 4 hours for NSE.

Conclusions: Critical pre-analytical processing step conditions were identified that, if not taken into account, will result in reporting of erroneous TM results.