The role of molecular studies in lymphoma diagnosis: a review

Spagnolo, Dominic V.; Ellis, David W.; Juneja, Surender; Leong, Anthony S.‐Y.; Miliauskas, John R.; Norris, Debra; Turner, Jennifer

doi:10.1080/00313020310001648404

Cited by 37 publications

(32 citation statements)

References 334 publications

(447 reference statements)

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“…Qualitative sensitivity is defined as the ability of the PARR assay to detect a purely clonal population of lymphocytes. 118 Quantitative or analytical sensitivity is defined as the assay's ability to detect a clonal rearrangement in a background of nonneoplastic lymphocytes. 55 In some cases, a neoplastic population of lymphocytes is present within an inflamed tissue, and the clonal lymphocytes can be, in effect, ''diluted out'' by the polyclonal inflammatory cells.…”

Section: Pcr To Detect Antigen Receptor Rearrangementsmentioning

confidence: 99%

Beyond H&E

et al. 2013

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Veterinary pathology of infectious, particularly viral, and neoplastic diseases has advanced significantly with the advent of newer molecular methodologies that can detect nucleic acid of infectious agents within microscopic lesions, differentiate neoplastic from nonneoplastic cells, or determine the suitability of a targeted therapy by detecting specific mutations in certain cancers. Polymerase chain reaction-based amplification of DNA or RNA and in situ hybridization are currently the most commonly used methods for nucleic acid detection. In contrast, the main methodology used for protein detection within microscopic lesions is immunohistochemistry. Other methods that allow for analysis of nucleic acids within a particular cell type or individual cells, such as laser capture microdissection, are also available in some laboratories. This review gives an overview of the factors that influence the accurate analysis of nucleic acids in formalin-fixed tissues, as well as of different approaches to detect such targets. Keywords cancer, ISH, IHC, nucleic acid analysis, molecular pathology, PCR, virology Technical ConsiderationsTissue Handling, Fixation, and Embedding Fixation of tissues in 10% neutral buffered formalin, followed by paraffin embedding (FFPE), has long been the standard approach of tissue preparation for microscopic evaluation. The chemical principle of formalin fixation is based on the crosslinking of proteins. Formalin has been used extensively because it is inexpensive and excellently preserves morphological detail in histological sections. However, the relatively recent development and increasing use of both protein and nucleic acid detection methods have revealed some significant shortcomings associated with the formalin-based fixation process. The effects of formalin fixation on DNA are chemical modification, DNA trapping, and potentially DNA fragmentation. Chemical modification, considered the main effect, results from the direct cross-linking of proteins to DNA. 68 In addition, extensive protein-protein cross-linking and the formation of protein networks result in DNA trapping. The combination of these effects makes it much more difficult to extract DNA from FFPE tissue than from unfixed tissue, especially when methods used for extraction from fresh tissues are used on FFPE tissue without any modifications. 60,83 In addition to interfering with the ability to extract nucleic acid, formalin fixation also causes DNA fragmentation, especially when the formalin used is inadequately buffered, which then leads to formic acid formation during the fixation process. This, in turn, results in depurination of the DNA, which then becomes susceptible to cleavage by hydroxyl ions and results in the formation of single-stranded breaks.60 Similar to DNA, RNA is also degraded and chemically modified as the result of formalin fixation. The most important chemical effect of formalin on RNA is the formation of monomethylol groups with purine bases. 77 This has a significant effect on reverse transcription ...

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Section: Pcr To Detect Antigen Receptor Rearrangementsmentioning

confidence: 99%

Beyond H&E

et al. 2013

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“…False negativity can be a consequence of DNA degradation, sampling errors, PCR assay design and choice of primer sets. In addition, postgerminal centre lymphomas, such as follicular lymphoma and marginal zone B-cell lymphomas, have a higher false negativity rate because of continuing somatic hypermutation, which impedes primer annealing [49,54] . Third, IgH and TCR gene rearrangements are not necessarily restricted to B-and T-cell lineages, respectively, and this lineage infidelity is another pitfall that might hamper interpretation [54,55] .…”

Section: Clonality Assessmentmentioning

confidence: 98%

“…Three distinct subtypes of diffuse large B-cell lymphoma (DLBCL) -germinal-center B-cell-like, activated B-cell-like and type 3 DLBCL -have been identified by GEP and a model predictive of outcome after chemotherapy could be derived [65,66] . Similarly, GEP of chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma and Burkitt's lymphoma have provided valuable information important for the understanding of pathogenesis, molecular diagnosis, prognostication and prediction of treatment response of these tumors [49,67] . In addition, new markers identified by GEP may be suitable targets for therapeutic intervention.…”

Section: Dna Microarray Analysis/gene Expression Profi Lingmentioning

confidence: 99%

“…The most common primary recurring genetic aberrations of non-Hodgkin's lymphomas are balanced chromosomal translocations leading to deregulation or activation of associated oncogenes, and this occurs by means of two different mechanisms [40,41,44,49,60] . Most commonly, the translocation juxtaposes the codifying region of an oncogene in one of the chromosomes to the regulatory region of a commonly expressed gene (e.g., Ig or TCR genes) in another chromosome.…”

Section: Detection Of Lymphoma-specifi C Chromosomal/genetic Abnormalmentioning

confidence: 99%

“…First, clonality does not necessarily equate with malignancy and the failure to detect clonality does not imply benignity. Second, false positive and false negative results can arise due to a combination of biological and technical factors, and errors of interpretation [49] . False positive results may be due to contamination and insufficient template DNA.…”

Section: Clonality Assessmentmentioning

confidence: 99%

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Detection of Clonal T Cells in the Circulation of Patients With Nephrogenic Systemic Fibrosis

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Background: Nephrogenic systemic fibrosis is a sclerodermalike disease in patients with acute or chronic renal insuffiency related to administration of gadoliniumcontaining contrast agents. Previous studies have demonstrated clonal T-cell populations in the blood of patients with systemic sclerosis, suggesting that these cells may be involved in the pathogenesis of the disease. Facing the clinical similarities of both diseases, we hypothesized that clonal expansion of T cells could be present in nephrogenic systemic fibrosis as well.

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The role of molecular studies in lymphoma diagnosis: a review

Cited by 37 publications

References 334 publications

Beyond H&E

Beyond H&E

The relevance of molecular diagnostics in the practice of surgical pathology

Detection of Clonal T Cells in the Circulation of Patients With Nephrogenic Systemic Fibrosis

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