Proper treatment of the patient with cancer depends on an accurate diagnosis of the tumor and is further directed by prognostic and more recently therapeutic molecular signatures in the era of precision medicine. Molecular oncology testing provides diagnostic, prognostic, and therapeutic information derived from the tumor genome. The aim of this review is to provide valuable information to laboratories for choosing optimal clinical specimens for molecular oncology testing by evaluating the strengths and weaknesses of different sample types from the procurement, processing, and pre-analytic selection matching to different test platforms.
Pathologists play a pivotal role in molecular oncology testing by providing oversight through the entire tissue journey.
Concurrently acquired core biopsy and fine-needle aspiration specimens are frequently complementary for both diagnosis and oncology testing, especially when paired with a rapid on-site evaluation.
Different types of specimens, including histology, cytology, and liquid biopsy, provide a wide variety of options to maximize the chance of testing success.
The main types of molecular oncology testing fall into three major categories: DNA-based, RNA-based, and protein-based assays.
Advances in our understanding of the molecular basis of cancer have led to the development of targeted therapies that are able to target specific alterations in the oncogenic pathway and can yield significant benefits to the patient’s overall and/or progression-free survival. Appropriate management of patients with solid organ and hematologic malignancies is frequently directed by molecular signatures that have necessitated molecular testing as part of the standard of care for these patients. Evaluation of the tumor biomarker profile through assessing nucleic acids and proteins can provide a detailed genomic map to guide precise individual treatment decisions. Molecular testing provides not only predictive, prognostic, and therapeutic information but also a snapshot of the genomic landscape of the tumor, allowing for monitoring the patient for tumor evolution, development of therapeutic resistance mechanisms, and detection of minimal residual disease.
Molecular oncology testing comes with several specific requirements for specimen collection, handling, and processing. The molecular oncology testing field is rapidly evolving with a growing number of clinically relevant biomarkers, shifting the focus from disease-specific single gene testing to broad panel-based tests that are capable of identifying alterations in myriad genes or their products. Being aware that different sample types possess specific advantages and limitations, the preanalytical variables due to sampling techniques, specimen preparation and processing methods, tumor heterogeneity and the advantages, and limitations of various testing methodologies can help the pathologist develop optimal strategies to maximize the utilization of valuable tissue specimens. Therefore, in this review, we summarize the strengths and weaknesses of different specimen types that are widely used in the clinical practice of molecular oncology testing. We hope to provide valuable information to laboratories in choosing optimal clinical specimens to achieve comprehensive molecular testing that formulates individually tailored treatment plans for patients with cancer.