MSACL 2025 Abstract

Critical High-Level Considerations for Quality Assurance in Imaging Mass Spectrometry: Lessons Learned from Immunohistochemistry

Emina Emilia Torlakovic, MD, PhD
College of Medicine and Canadian Biomarker Quality Assurance, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Emina Torlakovic, MD, PhD (Presenter) College of Medicine, University of Saskatchewan

Presenter Bio: Dr. Emina Emilia Torlakovic obtained her M.D. at the University of Zagreb Medical School and her Ph.D. at the University of Oslo Medical School. She is board certified by The American Board of Pathology in Anatomic and Clinical Pathology with subspecialty boards in Hematopathology. She is a professor at the Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, with previous appointment at the University of Toronto. She is a Division Head of Hematopathology, Saskatchewan Health Authority. She was a founding member of the NordiQC, has co-founded CIQC, and most recently founded Canadian Biomarker Quality Assurance (CBQA) as well as CBQAReadout.ca (inter)national academic quality assurance programs, which she is currently directing. Dr. Torlakovic is the Chair of the National Standards Committee for High Complexity Testing of the Canadian Association of Pathologists. She is the Past President of the International Society for Immunohistochemistry and Molecular Morphology (ISIMM) and a Board Member of the International Quality Network for Pathology (IQN Path). She is also currently leading several projects related to national and global standardization of biomarker testing in oncology.

Relevant Financial Disclosures (within past 24 months, reported on Aug 03, 2025) No relevant financial relationship(s) to disclose.

INTRODUCTION:
Validation of imaging mass spectrometry (IMS) frequently relies on immunohistochemistry (IHC) as the gold standard for confirming protein localization. However, cell-based in situ testing methodologies such as IHC, in situ hybridization (ISH), and IMS encounter distinct challenges, further compounded by diverse and often sub-optimally standardized pre-analytical variables.

DISCUSSION:
For decades, quality assurance (QA) in IHC was hindered by a limited understanding of the methodology. Key issues included:
i) misclassification of IHC—a qualitative assay—as a "semi-quantitative" laboratory test;
ii) the incorrect labeling of the pathologist’s (with or without image analysis) readout as an "interpretation" (post-analytical phase) rather than as a "readout" (analytical phase);
iii) failure to define and incorporate performance characteristics during assay development and validation;
iv) neglecting to align QA approaches with the ISO 9000 family of standards;
v) the absence of a “fit-for-purpose” strategy; and
vi) lack of reference materials and standards both for assay development and ongoing maintenance.
Drawing parallels with IHC is critical—not only because IHC serves as the gold standard for protein localization but also because, as cell-based in situ methodologies, both IHC and IMS share fundamental high-level QA challenges. Addressing these conceptual QA issues specific to cell-based in situ testing is essential for IMS before it can be broadly applied in clinical settings. Failure to timely resolve and globally standardize solutions to these QA concerns could significantly impede research, development, clinical implementation, and regulatory processes. Properly resolving these issues will help avoid both overregulation and underregulation of IMS by regulatory authorities worldwide.
This presentation will discuss how lessons from past shortcomings in IHC QA can inform the development of robust QA frameworks for IMS, thereby ensuring more effective and reliable clinical translation.