Prognostic significance of molecular staging by PCR-amplification of immunoglobulin gene rearrangements in diffuse large B-cell lymphoma (DLBCL)

Mitterbauer-Hohendanner, Gerlinde; Mannhalter, Christine; Winkler, Karin; Mitterbauer, Margit; Skrabs, Cathrin; Chott, Andreas; Simonitsch‐Klupp, Ingrid; Gleiß, Andreas; Lechner, Klaus; Jaeger, Ulrich

doi:10.1038/sj.leu.2403376

Cited by 37 publications

(48 citation statements)

References 37 publications

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“…As previously stated, in our study, diagnosis of BM involvement by either m-PTLD or p-PTLD was made based on strict morphologic and phenotypic criteria. While flow cytometry and molecular-based methods are highly sensitive in detecting BM involvement by lymphomas [24,33], these techniques are not well studied in PTLD; and the clinical implications of disease detection only by these more sensitive methods are not known in these patients. Therefore, these techniques were not used for determining BM involvement in our study.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow involvement in patients with posttransplant lymphoproliferative disorders: incidence and prognostic factors

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Bone marrow involvement in patients with posttransplant lymphoproliferative disorders: incidence and prognostic factors

et al. 2010

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“…The detection of identical T-or B-cell clones in a tissue sample and in PB is of great importance in staging lymphoid malignancies and is of prognostic relevance. [27][28][29][30] It should, however, be noted that the finding of (oligo)clonality might not always be clinically significant. (Oligo)clonal T-cell populations can be detected in PB of the elderly, 31,32 in patients diagnosed with autoimmune diseases, and in patients with viral infection.…”

Section: Discussionmentioning

confidence: 99%

BIOMED-2 Multiplex Immunoglobulin/T-Cell Receptor Polymerase Chain Reaction Protocols Can Reliably Replace Southern Blot Analysis in Routine Clonality Diagnostics

Sandberg

Gastel-Mol

Verhaaf

et al. 2005

The Journal of Molecular Diagnostics

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To establish the most sensitive and efficient strategy of clonality diagnostics via immunoglobulin and Tcell receptor gene rearrangement studies in suspected lymphoproliferative disorders, we evaluated 300 samples (from 218 patients) submitted consecutively for routine diagnostics. All samples were studied using the BIOMED-2 multiplex polymerase chain reaction (PCR) protocol. In 176 samples, Southern blot (SB) data were also available, and the two types of molecular results were compared. Results of PCR and SB analysis of both T-cell receptor and immunoglobulin loci were concordant in 85% of samples. For discordant results, PCR results were more consistent with the final diagnosis in 73% of samples. No false-negative results were obtained by PCR analysis. In contrast, SB analysis failed to detect clonality in a relatively high number of samples, mainly in cases of low tumor burden. We conclude that the novel BIOMED-2 multiplex PCR strategy is of great value in diagnosing patients with suspected B-and T-cell proliferations. Because of its higher speed, efficiency, and sensitivity, it can reliably replace SB analysis in clonality diagnostics in a routine laboratory setting. In most patients with suspected lymphoproliferative disorders, discrimination between reactive and malignant cell populations can be assessed by histomorphology or cytomorphology supplemented with immunohistochemistry or flow cytometric immunophenotyping. However, in 5 to 10% of patients, diagnosis is more complicated and less straightforward. In such cases, molecular gene rearrangement studies have proved useful as an additional diagnostic tool. Molecular clonality analysis is based on the fact that, in principle, all cells of a malignancy have a common clonal origin and show clonally (identically) rearranged immunoglobulin (Ig) or T-cell receptor (TCR) genes. The diagnosis of malignant B-and T-cell proliferations is therefore supported by the finding of Ig/TCR gene clonality, whereas reactive lymphoproliferations show polyclonally rearranged Ig/TCR genes. 1 Gene rearrangement analysis can be performed by Southern blot (SB)-and polymerase chain reaction (PCR)-based techniques. Despite the high reliability of SB analysis, it is increasingly replaced by PCR techniques because of the greater efficiency and sensitivity of PCR. Moreover, PCR is relatively easy, less labor intensive, and requires much less high-molecular-weight DNA. Also, SB analysis cannot be performed on paraffinembedded tissue because the isolated DNA is often degraded. Therefore, there is a strong need to replace SB analysis with reliable PCR techniques. However, PCR studies have often suffered from false-negative results due to improper annealing of primers and/or the presence of somatic hypermutation. 2 Both SB and PCR analyses of the immunoglobulin heavy chain (IGH) locus have been demonstrated to be very useful and reliable techniques in clonality assessment of suspected B-cell malignancies. However, the most useful gene target for identifying T-cell clonality is less well e...

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“…They found a significant difference in overall survival at 5 years in patients with negative histology and negative PCR results (66%), negative histology but positive PCR results (37%), and positive histology as well as positive PCR results (12%). 61 However, they used fresh peripheral blood and BM aspirate samples, and as discussed in previous sections, BM involvement in DLBCL is seen more often on trephine rather than aspirate samples. Previous reports have demonstrated that PCR results correlate better with trephine samples as compared to aspirate samples.…”

Section: Molecular Studies In Dlbclmentioning

confidence: 98%

Staging bone marrow in diffuse large B-cell lymphoma: the role of ancillary investigations

Talaulikar

Dahlstrom

2009

Pathology

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Prognostic significance of molecular staging by PCR-amplification of immunoglobulin gene rearrangements in diffuse large B-cell lymphoma (DLBCL)

Cited by 37 publications

References 37 publications

Bone marrow involvement in patients with posttransplant lymphoproliferative disorders: incidence and prognostic factors

Bone marrow involvement in patients with posttransplant lymphoproliferative disorders: incidence and prognostic factors

BIOMED-2 Multiplex Immunoglobulin/T-Cell Receptor Polymerase Chain Reaction Protocols Can Reliably Replace Southern Blot Analysis in Routine Clonality Diagnostics

Staging bone marrow in diffuse large B-cell lymphoma: the role of ancillary investigations

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