Role and prognostic significance of the Ki‐67 index in non‐Hodgkin's lymphoma

Broyde, Adi; Boycov, Olga; Strenov, Yulia; Okon, Elimelech; Shpilberg, Ofer; Bairey, Osnat

doi:10.1002/ajh.21406

Cited by 123 publications

(129 citation statements)

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“…Ki-67 is a valuable immunohistochemical marker to distinguish indolent from aggressive lymphomas, particularly in small needle biopsies where exact typing may not be possible (31). Several studies have demonstrated that high expression of Ki-67 is an adverse prognostic marker in systemic DLBCL (34)(35)(36). In the present study, it was also observed that Ki-67 expression is a significant prognostic parameter of poor prognosis in patients with PCNSL.…”

Section: Discussionsupporting

confidence: 63%

Immunohistochemical profile and prognostic significance in primary central nervous system lymphoma: Analysis of 89 cases

et al. 2017

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Abstract. The majority of primary central nervous system lymphomas (PCNSLs) are diffuse large B cell lymphoma, characterized by poor prognosis. In the present study, the expression of cluster of differentiation (CD)10, B cell lymphoma (BCL)-6, multiple myeloma-1 (MUM-1), BCL-2, CD138 and Ki-67 was analyzed by immunohistochemistry in 89 Chinese PCNSL cases, and the potential prognostic significance was evaluated. CD10, BCL-6, MUM-1, BCL-2 and CD138 were positive in 16.9 (15/89), 51.7 (46/89), 92.1 (82/89), 73.3 (63/86) and 0% (0/65) of all cases, respectively. According to the Hans algorithm, 71 patients (79.8%) were classified into the non-germinal center B cell-like (non-GCB) group, indicating a post-germinal center origin of PCNSL. The median follow-up time of 73 patients was 13 months [95% confidence interval (CI), 10.93-15.08]. The median overall survival (OS) time was 45.3 months (95% CI, 25.01-65.59) and the median progression-free survival (PFS) time was 30.0 months (95% CI, 13.43-46.57). Age (>60 years) was associated with a shorter OS time (P=0.009). Ki-67 (cutoff point 90%) was associated with shorter OS (P=0.037) and shorter PFS (P=0.039) times. No other immunohistochemical markers were associated with prognosis. On multivariate analysis, age (>60 years) was associated with shorter OS time (P=0.038), but immunophenotype and expression status of Ki-67, CD10, BCL-6 and BCL-2 did not predict prognosis. In conclusion, high Ki-67 expression may predict poor prognosis in PCNSL. The present study was limited by its sample size and short follow-up time. This requires more evidence to further clinical study.

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Section: Discussionsupporting

confidence: 63%

Immunohistochemical profile and prognostic significance in primary central nervous system lymphoma: Analysis of 89 cases

et al. 2017

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“…1 Many previous studies have shown that an increased PI in certain types of B-cell NHLs is associated with a more aggressive disease course. [2][3][4][5][6][7][8] These studies have been performed on diagnostic lymph nodes and other non-marrow tissues. We have encountered many requests for PI determination of the lymphoma on marrow specimens in cases where the marrow was the only diagnostic specimen.…”

Section: Introductionmentioning

confidence: 99%

Different expression of MIB1 in primary site of non-Hodgkin lymphoma and its bone marrow deposits, a pilot study

Malysz¹,

Evans²,

Acon-Laws³

et al. 2017

PLMI

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Evaluation of mindbomb E3 ubiquitin protein ligase 1 (MIB1) (Ki67) proliferation index (PI) in B-cell non-Hodgkin lymphomas is increasingly a common addition to classification of lymphoma and staging procedures. Clinicians relay on PI as a surrogate marker of biologic activity; however, no established guidelines have been published whether PI at the primary site of the tumor gives the same answer as evaluation of tumor in staging marrow. In our study, dual immunohistochemical staining for MIB1 and CD20 was performed on tissue from primary site and bone marrow involved by B-cell non-Hodgkin lymphoma to compare PI for each individual patient. For all patients, MIB1 expression was higher at primary tumor site as compared to staging marrow. Additional analysis was performed to investigate the degree of difference depending on lymphoma morphology. Patients with large cell lymphoma at the primary site and large cell morphology in the marrow (LCL-L), those with large cell morphology at the primary site and small cell morphology in the marrow (LCL-S), and those with small cell morphology at the primary site and small cells in the marrow (SCL-S) were compared. As expected, LCL cases had a higher mean PI at the primary site when compared to SCL cases (28.5% vs 2.8%, P=0.0001). In addition, the most significant difference between medullary and extramedullary PI was observed in cases with discordant morphology (LCL-S) (21% vs 1.1%, P=0.009). Our results indicate that PI of lymphoma within the bone marrow should not be used as a surrogate prognostic indicator of lymphoma biology in its primary site.

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“…Um marcador prognóstico bastante utilizado é o índice de proliferação celular, por meio da expressão de Ki-67, proteína nuclear que regula o ciclo celular e que pode ser reconhecida em todas as fases do ciclo mitótico, com exceção do G0, fase em que a célula não está se dividindo (FOURNEL-FLEURY et al, 1997b;GAMBICHLER et al, 2008;BROYDE et al, 2009;SOKOŁOWSKA et al, 2012). De acordo com Sokolowska et al (2012) podemos dividir a expressão de Ki-67 nos linfomas caninos de acordo com o número de células marcadas, como baixa (menos que 20%), média (de 21 a 50%) e alta (acima de 50%).…”

Section: Linfoma Cutâneo Caninounclassified

“…Tanto nos linfomas humanos quanto nos linfomas caninos, maior expressão de Ki-67 indica pior prognóstico (DUMMER et al, 1995;ABELE et al, 1997;FOURNEL-FLEURY et al, 1997b;BRYANT;BANKS;O'MALLEY, 2006;BROYDE et al, 2009;DUARTE, 2013;FLOOD-KNAPIK et al, 2013). Segundo alguns autores, alta expressão de Ki-67 é observada nas fases mais avançadas do linfoma cutâneo (DUMMER et al, 1995;GAMBICHLER et al, 2008;EDINGER et al, 2009 Apesar de ainda não haver protocolo estabelecido que controle o linfoma cutâneo a longo prazo, a quimioterapia com a lomustina parece ter maior índice de resposta e maior duração, quando comparada a outros protocolos de tratamento (RISBON et al, 2006;WILLIAMS et al, 2006;LAPRAIS;OLIVRY, 2017).…”

Section: Linfoma Cutâneo Caninounclassified

“…anos e a média de sobrevida é de 5 a 10 meses para os linfomas epiteliotrópicos e de 4 meses para os não-epiteliotrópicos GROSS et al, 2005;MOORE et al, 2009;MILLER;GRIFFIN;CAMPBELL, 2013;DIAS et al, 2015) indicando que os linfomas cutâneos são mesmo mais frequentes em animais mais velhos e têm um mau prognóstico com relação ao tempo de sobrevida (MOORE et al, 2009;MILLER;GRIFFIN;CAMPBELL, 2013), embora a sobrevida observada ainda tenha sido um pouco maior do que aquela observada em 29 animais, no interior do Estado, por Hernandez, 2017. As lesões apresentadas pelos animais estudados com diagnóstico de linfoma epiteliotrópico foram majoritariamente generalizadas, na forma de nódulos ulcerados, sendo que alguns animais apresentaram pápulas eritematosas, crostas, e despigmentação, o que está de acordo com o descrito por outros autores (GROSS et al, 2005;FONTAINE et al, 2009;MILLER;GRIFFIN;CAMPBELL, 2013 Quanto à agressividade do processo, a proteína relacionada à proliferação celular Ki67, tem sido utilizada como um marcador prognóstico nos linfomas, sendo que sua maior expressão indica maior proliferação celular e pior prognóstico (DUMMER et al, 1995;ABELE et al, 1997;FOURNEL-FLEURY et al, 1997b;BRYANT;BANKS;O'MALLEY, 2006;GAMBICHLER et al, 2008;BROYDE et al, 2009;DUARTE, 2013;FLOOD-KNAPIK et al, 2013). Neste estudo, observou-se mediana de expressão de Ki67 de 31%.…”

Section: íNdice De Proliferação Celular -Expressão De Ki67unclassified

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<b>Estudo da expressão imunoistoquímica de marcadores de resistência a múltiplas drogas em cães com linfoma cutâneo</b>

Alves¹

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Among mechanisms of resistance are efflux of drugs from intracellular to extracellular through ABC family transporters such as P-glycoprotein, MRP (multple resistance protein) and BCRP (breast cancer resistance protein) and LRP (lung resistance protein), a vault protein responsible for nucleocytoplasmic transport. The aim of this study was to characterize immunophenotypically cutaneous lymphomas, measure cell proliferation using the Ki67 marker, the expression of resistance proteins Pglycoprotein, MRP, BCRP and LRP and to evaluate the relationship of these proteins with the survival of the animals. A retrospective study was performed with 21 cases of dogs with cutaneous lymphoma with histopathological diagnosis.Immunohistochemical was used to immunophenotyping of lymphomas by CD3 and CD20 markers, Ki67 cell proliferation, and P-glycoprotein, MRP, BCRP and LRP expression. Of the 21 animals, 38% had histopathological diagnosis of epitheliotropic lymphoma, 52% were non-epitheliotropic lymphomas, 5% of lymphoma cases had no definition and 5% were classified as round cell neoplasia. The predominant immunophenotype was CD3+CD20-(76%), 15% of the cases were CD3-CD20 + and 9% were CD3 + CD20 +. The median of cells labeled for Ki67 was 31%. Regarding the markers of resistance to multiple drugs, the median of the P-glycoprotein label was 40%, which 65% of LRP while for MRP and BCRP, 19% and 23%, respectively. Non-epitheliotropic cutaneous lymphomas were more frequent than epitheliotropic lymphomas and the predominant immunophenotype was T. The occurrence of CD3-CD20+ and CD3+CD20+ lymphocytes indicates the need for further studies and a wider panel of antibodies for subtyping these lymphomas. P-glycoprotein had higher expression in non-epitheliotropic lymphomas than in epitheliotropic lymphomas and there was no correlation between resistance proteins and survival time of the animals, suggesting that in addition to the biology of neoplasia other mechanisms of resistance to multiple drugs different from those studied may play a relevant role in the low response of cutaneous lymphoma to chemotherapy.

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Role and prognostic significance of the Ki‐67 index in non‐Hodgkin's lymphoma

Cited by 123 publications

References 25 publications

Immunohistochemical profile and prognostic significance in primary central nervous system lymphoma: Analysis of 89 cases

Immunohistochemical profile and prognostic significance in primary central nervous system lymphoma: Analysis of 89 cases

Different expression of MIB1 in primary site of non-Hodgkin lymphoma and its bone marrow deposits, a pilot study

<b>Estudo da expressão imunoistoquímica de marcadores de resistência a múltiplas drogas em cães com linfoma cutâneo</b>

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