MYC protein expression scoring and its impact on the prognosis of aggressive B-cell lymphoma patients

Ambrosio, Maria Raffaella; Lazzi, Stefano; Bello, Giuseppe; Santi, Raffaella; Porro, Leonardo Del; Santi, Maria Margherita De; Guazzo, Raffaella; Mundo, Lucia; Rigacci, Luigi; Kovalchuck, Sofia; Onyango, Noel; Fabbri, Alberto; Cencini, Emanuele; Zinzani, Pier Luigi; Zaja, Francesco; Angrilli, Francesco; Stelitano, Caterina; Cabras, Maria Giuseppina; Spataro, Giuseppe; Bob, Roshanak; Menter, Thomas; Granai, Massimo; Cevenini, Gabriele; Naresh, Kikkeri N.; Stein, Harald; Sabattini, Elena; Leoncini, Lorenzo

doi:10.3324/haematol.2018.195958

Cited by 35 publications

(41 citation statements)

References 15 publications

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“…The majority were treated with R‐CHOP (85%) and in multivariable Cox regression analysis IPI, R‐CHOP‐like treatment and MYC translocation combined with high MYC expression levels (trends) were the only factors with possible prognostic impact. Similar findings of a highly prognostic impact of high MYC expression in patients with DH were also recently described in a large retrospective cohort including 51 patients with DH lymphoma treated with R‐CHOP or R‐CHOP‐like regimens . Together, these findings challenge the general opinion that DH MYC/BCL2 translocation per se confers a poor prognosis and could lend explanation to reports of long‐term survival in patients with MYC or DH translocation positive LBCL …”

Section: Discussionsupporting

confidence: 82%

“…So-called single hit MYC translocation (SH) without concurrent BCL2 and/or BCL6 rearrangements has also been associated with inferior survival, [2][3][4][5][6] and in addition, we and others described particularly poor outcome both in patients with MYC-SH or DH with an immunoglobulin-(IG) MYC translocation partner gene. [7][8][9][10] In addition, stratification of patients with MYC-SH and DH translocations according to MYC protein expression level 11,12 and/or BCL2 expression level 9,10 has been suggested to impact patient survival in few studies.…”

Section: Introductionmentioning

confidence: 99%

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Stratification by MYC expression has prognostic impact in MYC translocated B‐cell lymphoma—Identifies a subgroup of patients with poor outcome

Pedersen

Gang

Clasen‐Linde

et al. 2019

European J of Haematology

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Objective In patients with large B‐cell lymphoma (LBCL) according to WHO, the prognostic significance of MYC translocation is still not sufficiently clarified. We therefore aimed to investigate whether prognostication could be improved in patients with MYC translocation positive LBCL by additional stratification according to MYC and BCL2 protein expression levels or MYC translocation partner gene as well as concurrent BCL2 and/or BCL6 translocation (DH). Methods From an unselected consecutive cohort of >600 patients with LBCL investigated with fluorescent in situ hybridization (FISH), 64 patients were diagnosed with MYC translocation positive LBCL and included in the study. They were further investigated for supplemental translocations with FISH and MYC and BCL2 protein expression with immunohistochemistry (IHC). Results MYC expression >75% was associated with both reduced progression‐free survival (PFS) and overall survival (OS) (PFS: HR 6.8 (95% CI 1.5‐31), P = 0.004. OS: HR 4.3 (95% CI 0.9‐21), P = 0.05). Immunoglobulin (IG) MYC translocation partner gene was related to high MYC protein expression (P = 0.047) but was not prognostic for PFS (P = 0.8) or OS (P = 0.6). DH did not confer a worse outcome compared to MYC single hit (SH). These findings were confirmed in a comparable, independent validation cohort of 28 patients with MYC translocation positive LBCL. All patients included in the survival analyses were treated with R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R‐CHOEP (R‐CHOP + etoposide). Conclusion These findings suggest that in patients with LBCL stratification by MYC protein expression level significantly improves the prognostic impact associated with MYC translocation.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Stratification by MYC expression has prognostic impact in MYC translocated B‐cell lymphoma—Identifies a subgroup of patients with poor outcome

Pedersen

Gang

Clasen‐Linde

et al. 2019

European J of Haematology

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“…We selected BCL2 and MYC as candidates for predictors because numerous studies on DLBCL have reported their association with poor prognosis (9,35,36). Although the proportions of 40 and 50% were generally considered as cut-off points for positivity in MYC and BCL2 IHC, respectively (2), it was mostly dependent on visual observation, and there have been controversies regarding various proportional cut-off points (36,37). Therefore, we employed a digital quantitative acquisition and analysis for the objective measurements of BCL2 and MYC expressions without dichotomization.…”

Section: Quantitative Analysis Of Biomarker Expressionmentioning

confidence: 99%

Risk Stratification Using Multivariable Fractional Polynomials in Diffuse Large B-Cell Lymphoma

et al. 2020

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The risk stratification of diffuse large B-cell lymphoma (DLBCL) is crucial. The International Prognostic Index, the most commonly used and the traditional risk stratification system, is composed of fixed and artificially dichotomized attributes. We aimed to develop a novel prognostic model that allows the incorporation of up-to-date attributes comprehensively without information loss. We analyzed 204 patients with primary DLBCL who were uniformly treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) from 2007 to 2012 at Asan Medical Center. Using the multivariable fractional polynomial (MFP) method and bootstrap resampling, we selected the variables of significance and the best fitted functional form in fractional polynomials. Age, serum β2-microglobulin, serum lactate dehydrogenase, and BCL2 expression were selected as significant variables in predicting overall survival (OS), while age was excluded in predicting 2-years event-free survival. The prognostic score calculated by the MFP model effectively classifies patients into four risk groups with 5-years OS of 89.91% (low risk), 81.21% (low-intermediate risk), 66.40% (high-intermediate risk), and 37.89% (high risk). We suggest a new prognostic model that is simple and flexible. By using the MFP method, we can incorporate various clinicopathologic factors into a risk stratification system without arbitrary dichotomization.

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“…Whenever a B cell lymphoma with a DLBCL morphology displays either a GCB COO and/or a double expression of MYC and BCL2 proteins (in more than 40% and 50% of neoplastic cells, respectively) (DE DLBCL), analysis of MYC , BCL2 , and BCL6 gene rearrangements by FISH is indicated in order to rule out the possibility of a HGBL DH/TH. Although there is no complete agreement about the percentage of MYC protein-expressing cells that accurately predicts the presence of MYC gene rearrangement [6, 9, 10], the cutoff value of 70% has been recently reported to be reproducible among different centers and of clinical value in identifying patients with a worse prognosis [7].…”

Section: Diagnostic Workflowmentioning

confidence: 99%

A practical algorithmic approach to mature aggressive B cell lymphoma diagnosis in the double/triple hit era: selecting cases, matching clinical benefit

Napoli¹,

Remotti

Agostinelli³

et al. 2019

Virchows Arch

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An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient.

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MYC protein expression scoring and its impact on the prognosis of aggressive B-cell lymphoma patients

Cited by 35 publications

References 15 publications

Stratification by MYC expression has prognostic impact in MYC translocated B‐cell lymphoma—Identifies a subgroup of patients with poor outcome

Stratification by MYC expression has prognostic impact in MYC translocated B‐cell lymphoma—Identifies a subgroup of patients with poor outcome

Risk Stratification Using Multivariable Fractional Polynomials in Diffuse Large B-Cell Lymphoma

A practical algorithmic approach to mature aggressive B cell lymphoma diagnosis in the double/triple hit era: selecting cases, matching clinical benefit

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