Proliferation centers in chronic lymphocytic leukemia: correlation with cytogenetic and clinicobiological features in consecutive patients analyzed on tissue microarrays

Ciccone, Maria; Agostinelli, Claudio; Rigolin, Gian Matteo; Piccaluga, Pier P.; Cavazzini, Francesco; Righi, Simona; Sista, Maria Teresa; Sofritti, Olga; Rizzotto, Lara; Sabattini, Elena; Fioritoni, Giuseppe; Falorio, Simona; Stelitano, Caterina; Olivieri, Attilio; Attolico, Immacolata; Brugiatelli, Maura; Zinzani, Pier Luigi; Saccenti, Elena; Capello, Daniela; Negrini, Massimo; Cuneo, Antonio; Pileri, Stefano

doi:10.1038/leu.2011.247

Cited by 59 publications

(43 citation statements)

References 45 publications

(55 reference statements)

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“…For years, researchers believed that the extent of PCs was associated with worse prognosis since PCs are metabolically and mitotically active zones. So far, however, only a limited number of studies showed findings that supported this hypothesis [18], while others usually failed to demonstrate a correlation between the extent of PCs and prognosis [19,20,21]. In our study, we also could not show a significant correlation.…”

Section: Discussioncontrasting

confidence: 84%

TP53 Staining in Tissue Samples of Chronic Lymphocytic Lymphoma Cases: An Immunohistochemical Survey of 51 Cases

Kulaç

Demir²,

Büyükaşık³

et al. 2017

Tjh

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Objective:Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disease in adults. The aim of this study is to find out if the extent of proliferation centers or the immunohistochemical expression of p53 is related to disease prognosis.Materials and Methods:In the scope of this study, 54 biopsy specimens from 51 patients (50 of lymph nodes; the others of spleen, tonsil, orbit, and liver) diagnosed with CLL at the Hacettepe University Department of Pathology in 2000-2013 were reevaluated. The clinical and demographic data of the patients were obtained from our patient database. Biopsy samples were assessed semi-quantitatively for the percentage of proliferation center/total biopsy area (PC/TBA) and an immunohistochemical study was performed on representative blocks of tissues for p53 expression.Results:When the patients were divided into two categories according to Rai stage as high and low (stages 0, 1, and 2 vs. stages 3 and 4), it was seen that patients with low Rai stage had a better prognosis than those with high stages (p=0.030). However, there was no statistically significant correlation between overall survival and PC/TBA ratio or p53 expression levels.Conclusion:In our cohort, PC/TBA ratio and immunopositivity of p53 did not show correlations with overall survival.

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Section: Discussioncontrasting

confidence: 84%

TP53 Staining in Tissue Samples of Chronic Lymphocytic Lymphoma Cases: An Immunohistochemical Survey of 51 Cases

Kulaç

Demir²,

Büyükaşık³

et al. 2017

Tjh

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“…Taken together, these findings suggest that a high FDG uptake could identify cases of CLL with a more pronounced proliferation pattern and aggressive disease. A high rate of Ki-67 positive cells associated with large proliferation centers has been described in the lymph node biopsies of patients with a more aggressive form of the CLL termed as "accelerated CLL" (6)(7)(8). In this study, a SUV max value of ≥5 was associated with an unfavorable outcome both in treatment naïve and in previously treated patients with CLL.…”

Section: Discussionmentioning

confidence: 64%

“…An aggressive diffuse large Bcell lymphoma (DLBCL) and, less frequently, a Hodgkin"s lymphoma (HL) are the most commonly observed forms of disease transformation, defined as Richter"s syndrome (RS) (3)(4)(5). In addition, clinically aggressive forms of CLL characterized by a high proliferation index have also been described (6)(7)(8). Since the presence of enlarged "bulky nodes", as well as the observation of extra-nodal lesions, can lead both to the suspicion of a CLL progression and to the possibility of a RS or a SM, a biopsy of the involved tissue is the only appropriate approach for a correct diagnostic work-up.…”

Section: Introductionmentioning

confidence: 98%

Diagnostic and prognostic role of PET/CT in patients with chronic lymphocytic leukemia and progressive disease

et al. 2015

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In order to evaluate the predictive value of positron emission tomography-computed tomography (PET/CT) in discriminating the presence of a Richter's syndrome (RS) or a second malignancy (SM), as well as to evaluate its prognostic value in patients with chronic lymphocytic leukemia (CLL), we retrospectively analyzed the data of 90 patients who, in the suspicion of a RS or a SM, underwent PET/CT followed by the biopsy of the involved tissue. The median maximum Standardized Uptake Value (SUV max) in the presence of a CLL/small lymphocytic lymphoma, a diffuse large B-cell lymphoma (DLBCL), a Hodgkin lymphoma (HL), a SM were 3.5, 14.6, 7.0 and 6.3, respectively (P ⩽ 0.0001). A SUV max cutoff value ⩾ 5 showed a sensitivity, specificity, positive and negative predictive values of 88.2, 71.2, 51.3 and 94%, respectively, for the presence of a more aggressive disease (DLBCL, HL and SM). A SUV max ⩾ 5 identified also a subset of treatment naive patients with an inferior progression-free survival (P = 0.011) and overall survival (P = 0.067). These findings suggest that PET/CT may helpfully integrate the biologically-based prognostic stratification of CLL. Prospective clinical trials including larger cohorts of patients are needed to conclusively define the role and prognostic impact of PET/CT in the routine management of CLL patients.

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“…As a consequence, the natural history of the disease is dictated, in part, by lymphocyte survival and growth in the lymph nodes that favours the accumulation of genomic alterations, especially within proliferation centres and/or CD38-positive cells 24,25. Biomarkers reflecting the capability to respond to BCR engagement or to adhere to niches in the bone marrow or lymph node (i.e.…”

Section: Resultsmentioning

confidence: 99%

“Identifying High-Risk Chronic Lymphocytic Leukemia: A Pathogenesis-Oriented Appraisal of Prognostic and Predictive Factors in Patients Treated With Chemotherapy With or Without Immunotherapy.”

Martinelli

Cuneo

Rigolin

2016

Mediterr J Hematol Infect Dis

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Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment are important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers. Each biomarker was analysed in terms of reproducibility across the different studies with respect to its impact on time to first treatment (TTFT), progression free survival (PFS), overall survival (OS) and response to treatment. We were able to identify the following biomarkers as the most reliable in guiding risk stratification in the daily clinical practice: 17p-/TP53 mutations, IGHV unmutated configuration, short telomeres and 11q-. However, the method for measuring telomere length was not validated yet and 11q- was predictive of inferior OS only in those patients who did not receive FCR-like combinations. Stage and lymphocytosis were predictive of shorter TTFT and age, high serum thymidine kinase levels and poor performance status were predictive of shorter OS. Using our criteria no parameter was found to independently predict for inferior response to treatment.

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Proliferation centers in chronic lymphocytic leukemia: correlation with cytogenetic and clinicobiological features in consecutive patients analyzed on tissue microarrays

Cited by 59 publications

References 45 publications

TP53 Staining in Tissue Samples of Chronic Lymphocytic Lymphoma Cases: An Immunohistochemical Survey of 51 Cases

TP53 Staining in Tissue Samples of Chronic Lymphocytic Lymphoma Cases: An Immunohistochemical Survey of 51 Cases

Diagnostic and prognostic role of PET/CT in patients with chronic lymphocytic leukemia and progressive disease

“Identifying High-Risk Chronic Lymphocytic Leukemia: A Pathogenesis-Oriented Appraisal of Prognostic and Predictive Factors in Patients Treated With Chemotherapy With or Without Immunotherapy.”

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