Low versus high cell turnover in diffusely growing non‐Hodgkin's lymphomas

Spina, Donatella; Leoncini, Lorenzo; Vecchio, Maria Teresa Del; Megha, Tiziana; Minacci, Chiara; Poggi, Simonetta; Piler, Stefano; Tosi, Piero; Kraft, Rainer; Laissue, Jean A.; Cottier, H.

doi:10.1002/path.1711770403

Cited by 28 publications

(21 citation statements)

References 14 publications

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“…In one study, tumor kinetic variables were combined in a fashion that demonstrated the predictive value of a novel parameter termed the turnover index (the sum of the mitotic index and apoptotic index). 35 In that study, a group of patients with high-grade nonHodgkin's lymphoma and with low turnover index had significantly longer overall survival time than the group with high turnover index. It is conceivable that apoptosis and proliferation are coupled and that tumor growth occurs when apoptosis is prevented.…”

Section: Discussionmentioning

confidence: 96%

Apoptotic and Proliferation Indexes in Canine Lymphoma

et al. 2000

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Proliferative and apoptotic fractions of tumors were evaluated in 41 dogs with lymphoma for prediction of response to chemotherapy. All dogs had advanced clinical stage tumors, were untreated prior to study, and received identical induction-remission chemotherapy. Tumor cell proliferation was determined in all pretreatment biopsy specimens and in 18 specimens collected at the time of clinical relapse from remission. Quantitative measures included mitotic index and immunoreactivities for proliferating cell nuclear antigen (PCNA) and Ki-67. Apoptotic index was evaluated from 40 dogs pretreatment and from 16 dogs at the time of first relapse. Pretreatment tumor values for Ki-67, PCNA, and apoptosis were compared with posttreatment values. The median first relapse-free interval (RFI) and overall survival (OS) time were 174 days and 445 days, respectively. Of the proliferation markers, only the results of the Ki-67 analysis were predictive for duration of the first RFI but not OS. Pretreatment apoptotic index was also predictive of the duration of first RFI but not OS. No significant predictive value for comparison of the pretreatment and postrelapse values was demonstrated. Ki-67 labeling index and apoptotic indexes were combined to form both a proliferation/apoptotic ratio (PAR) and a sum, or turnover index. Only the PAR was predictive for duration of first RFI on multivariate analysis. Other variables that were evaluated for their influence on treatment outcome included patient age, weight, gender, clinical stage, clinical substage, and tumor immunophenotype. Of these variables, only immunophenotype was found to be of value for predicting duration of first RFI and OS.

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Section: Discussionmentioning

confidence: 96%

Apoptotic and Proliferation Indexes in Canine Lymphoma

et al. 2000

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“…In this context, stimulating investigations to determine the dynamics of cell turnover have been carried out. However, evaluations between apoptotic and proliferative indices has been limited exclusively to malignant lymphomas so far [15,16,35,36,53]. For this reason, the present study was concentrated on the issue of whether reactive and neoplastic lesions of the bone marrow with extreme ranges of cell production -as reflected by cor- responding laboratory data -may also be characterized by significantly different turnover rates of hematopoiesis.…”

Section: Introductionmentioning

confidence: 97%

Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling

Thiele

Zirbes

Lorenzen

et al. 1997

Annals of Hematology

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In order to determine the dynamics of hematopoietic cell turnover, proliferative activity and incidence of apoptosis (programmed cell death) were evaluated in bone marrow trephine biopsies. Selection of patients (20 in each group) included in addition to a control group, idiopathic thrombocytopenia (ITP), reactive thrombocytosis (TH), secondary polycythemia-smokers' polyglobuly (PG), primary (essential-hemorrhagic) thrombocythemia (PTH), polycythemia vera (PV), and finally acute myeloid leukemia (AML). Apoptosis was demonstrated by the in situ end-labeling technique (ISEL) and proliferative activity by applying the monoclonal antibody PC10 raised against proliferating cell nuclear antigen (PCNA). To assess dynamic features of hematopoiesis, an index was calculated consisting of the ratio between PCNA-positive nuclei and the apoptotic cell fraction. This factor was termed the hematopoietic turnover index (HTI). Morphometric analysis revealed that the HTI was significantly increased in AML and PV. According to cell culture studies both disorders are characterized by either a prevalent proliferation of the myeloid or erythroid cell mass. On the other hand, PG, PTH, and TH showed no relevant enhancement of this index in comparison to the control specimen. In vitro experiment results are in keeping with the finding that PG and PTH are not associated with a significant expansion of the erythroid lineage (CFU-E). Similar to ITP and TH, in PTH megakaryocyte proliferation (CFU-MEG) is the predominant feature of cell turnover. Differences between PTH and TH are in line with the reduced in vitro formation of CFU-MEG in the latter disorder. In conclusion, our in situ study on turnover rates of the bone marrow in various neoplastic and reactive lesions extends previous experimental data on hematopoietic cell kinetics.

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“…On these slides, MI and AI were registered blindly by 2 experienced pathologists, based on counts in 30 randomly chosen high-power fields (6,000-9,000 cells per case), as described (Del Vecchio et al, 1991;Leoncini et al, 1993). This counting technique has proved to be associated with a high inter-observer reproducibility (correlation coefficient Ͼ0.95; Miracco et al, 1993) and results correlate well (r ϭ 0.89; Spina et al, 1995) with those obtained from in situ end-labeling of DNA to demonstrate strand breaks (Ansari et al, 1993). …”

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confidence: 66%