Preanalytics and Precision Pathology: Pathology Practices to Ensure Molecular Integrity of Cancer Patient Biospecimens for Precision Medicine

Abstract

Biospecimens acquired during routine medical practice are the primary sources of molecular information about patients and their diseases that underlies precision medicine and translational research. In cancer care, molecular analysis of biospecimens is especially common because it often determines treatment choices and may be used to monitor therapy in real time. However, patient specimens are collected, handled, and processed according to routine clinical procedures during which they are subjected to factors that may alter their molecular quality and composition. Such artefactual alteration may skew data from molecular analyses, render analysis data uninterpretable, or even preclude analysis altogether if the integrity of a specimen is severely compromised. As a result, patient care and safety may be affected, and medical research dependent on patient samples may be compromised. Despite these issues, there is currently no requirement to control or record preanalytical variables in clinical practice with the single exception of breast cancer tissue handled according to the guideline jointly developed by the American Society of Clinical Oncology and College of American Pathologists (CAP) and enforced through the CAP Laboratory Accreditation Program. Recognizing the importance of molecular data derived from patient specimens, the CAP Personalized Healthcare Committee established the Preanalytics for Precision Medicine Project Team to develop a basic set of evidence-based recommendations for key preanalytics for tissue and blood specimens. If used for biospecimens from patients, these preanalytical recommendations would ensure the fitness of those specimens for molecular analysis and help to assure the quality and reliability of the analysis data.

The leading role of pathology in assessing the somatic molecular alterations of cancer: Position Paper of the European Society of Pathology

“…Technical issues are important to obtain correct results [26][27][28][29][30]. Pathology departments are responsible for providing the appropriate pre-analytical conditions which are crucial to get correct results.…”

Minimum Technical Data Elements for Liquid Biopsy Data Submitted to Public Databases

“…The collection, handling, and processing of biospecimens have long been recognized to contribute to assay variability and challenges of assay validation. [3][4][5][6][7][8] In fact, overlooking preanalytical variables can have negative consequences for diagnostic development. 9 In the context of assay development, the preanalytical steps pertain to everything related to the sample before any assay is run.…”

Mutational Screening of BRCA1/2 Genes as a Predictive Factor for Therapeutic Response in Epithelial Ovarian Cancer: A Consensus Guide from the Spanish Society of Pathology (SEAP-IAP) and the Spanish Society of Human Genetics (AEGH)

“…To limit this effect, standard procedures in tissue preservation in fixative process or freezing in optimum cutting temperature (OCT) compound are recommended for optimum DNA recovery. However, DNA is more frequently isolated from formalin-fixed paraffin-embedded (FFPE) samples and is highly recommended that the tissue fixation procedure be controlled by the pathology laboratory [18,59,68] [57,61] [22]. Finally, morphological diagnosis should always include the type and grade of the tumors in order to gain insight into genotypic/phenotypic correlations.…”