Abstract
The diagnosis of benign and malignant soft tissue and bone neoplasms is a challenging area of surgical pathology, due to the large number, rarity, and histologic diversity of tumor types. In recent years, diagnosis and classification has been aided substantially by our growing understanding of recurrent molecular alterations in these neoplasms. Concurrently, the role of diagnostic immunohistochemistry has also expanded, with the development of numerous biomarkers based on underlying molecular events. Such biomarkers allow us to infer the presence of these events and can therefore substitute for other ancillary molecular genetic techniques (e.g., fluorescence in situ hybridization, polymerase chain reaction, and next-generation sequencing). In this review, we discuss a range of biomarkers currently available for these neoplasms, highlighting the accuracy, staining characteristics, and interpretation pitfalls of each antibody. These include immunohistochemical antibodies that represent reliable surrogates for the detection of gene fusions (e.g., STAT6, CAMTA1, FOSB, DDIT3) and more recently described breakpoint-specific antibodies (e.g., SS18-SSX, PAX3/7-FOXO1). Additionally, discussed are markers that correlate with the presence of gene amplifications (e.g., MDM2, CDK4), deletions (e.g., SMARCB1, SMARCA4), single nucleotide variants (e.g., G34W, K36M), aberrant methylation (H3K27me3), and increased expression as discovered through gene expression profiling (e.g., MUC4, DOG1, ETV4, NKX2.2, NKX3.1).
Highlights
Sarcomas are a large and heterogeneous group of malignant mesenchymal neoplasms, comprising at least 70 distinct types, which together account for around 1% of all cancers [1].The diagnosis of sarcomas can be challenging, due in part to the rarity of each tumor type, their remarkable histologic diversity, and the frequent use of limited biopsy material.Despite these challenges, correct classification remains crucially important for patient management, prognostication, and research efforts.In the last three decades, a broad repertoire of molecular events has been characterized in sarcomas
The molecular diagnosis of Solitary fibrous tumor (SFT) did not become straightforward, since NAB2-STAT6 is generated by a small paracentric inversion of 12q13 that cannot be detected by fluorescence in situ hybridization (FISH), while the variable breakpoints make reverse transcriptasepolymerase chain reaction (RT-PCR) laborious
FOSB is a useful biomarker for epithelioid hemangioma, a separate vascular neoplasm that behaves in a benign fashion [53]
Summary
Sarcomas are a large and heterogeneous group of malignant mesenchymal neoplasms, comprising at least 70 distinct types, which together account for around 1% of all cancers [1]. In the last three decades, a broad repertoire of molecular events has been characterized in sarcomas Many of these are found recurrently and consistently in certain tumor types, allowing ancillary genetic tests to become very helpful in the diagnosis of difficult cases. Immunohistochemistry—a more rapid, relatively inexpensive, and widely available technique—has continued to evolve and remain at the forefront of sarcoma diagnostics In recent years, this has largely been due to a wave of new biomarkers, able to detect the protein products of specific genetic alterations and thereby clearly exploit our growing understanding of molecular pathology. This has largely been due to a wave of new biomarkers, able to detect the protein products of specific genetic alterations and thereby clearly exploit our growing understanding of molecular pathology For many sarcomas, this approach is affording more precise immunohistochemical diagnosis than was possible with earlier markers which generally aim to establish line of differentiation.
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