Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays

Garcı́a, Juan F.; Camacho, Francisca I.; Morente, Manuel; Fraga, Máximo; Montalbán, Carlos; Álvaro, Tomás; Bellas, Carmen; Castaño, Ángel; Díez, Ana; Flores, Teresa; Martín, Carmen; Martı́nez, Miguel Ángel; Mazorra, Francisco; Menárguez, Javier; Mestre, María J.; Mollejo, Manuela; Sáez, Ana I.; Sánchez, Lydia; Piris, Miguel Á.

doi:10.1182/blood-2002-04-1128

Cited by 219 publications

(217 citation statements)

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“…In contrast to our data, Garcia et al 22 and Ohshima et al 25 reported higher expression of p27 KIP1 and p21 CIP1 in their classical Hodgkin's lymphoma samples. However, Garcia et al applied other primary anti-p27 KIP1 antibodies, and Ohshima et al determined the expression of p21 CIP1 on frozen classical Hodgkin's lymphoma tissue samples, which might explain some of the differences.…”

Section: Discussioncontrasting

confidence: 99%

“…Because PCNA is mainly expressed in S-phase cells, we conclude that the majority of Hodgkin and ReedSternberg cells are either in S-or G 2 -phase of the cell division cycle. Our data confirm previously published data [2][3][4]22,24 reporting high expression of PCNA and Ki-67 in classical Hodgkin's lymphoma.…”

Section: Discussionsupporting

confidence: 92%

“…Several proteins that regulate the mitotic cycle, such as cyclin D1, D3, E, B1, cyclin-dependent kinases 1, 2 and 6, S-phase kinase associated protein-2, p16 INK4A , p18 INK4c , p21 CIP1 , p27 KIP1 , p53, the retinoblastoma protein and PCNA have been found to be deregulated in classical Hodgkin's lymphoma. [1][2][3][4]6,[20][21][22][23][24][25][26] In the present study, we used a previously validated classical Hodgkin's lymphoma tissue microarray with a cohort of clinically well-documented cases 6,17,27 to analyze the expression of the cyclin-dependent kinase inhibitors of the Cip/Kipfamily, p21 CIP1 and p27 KIP1 , as well as two proliferation markers, PCNA and cyclin A. Since Hodgkin and Reed-Sternberg cells are embedded within reactive normal lymphocytes, we used those lymphocytes as internal controls for our staining Aberrant cell cycle regulation in Hodgkin's lymphoma A Tzankov et al conditions.…”

Section: Discussionmentioning

confidence: 99%

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Aberrant expression of cell cycle regulators in Hodgkin and Reed–Sternberg cells of classical Hodgkin's lymphoma

et al. 2005

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The characteristic Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma, although highly positive for proliferation markers, do not accumulate to excessive cell numbers. These cells are characterized by abortive mitotic cycles, leading to multinucleation or cell death in mitosis. We have previously described high expression of G 1 -phase cyclins in classical Hodgkin's lymphoma, which could explain the high percentage of cells staining for proliferation markers. To further our understanding of proliferation control in classical Hodgkin's lymphoma, we extended our immunohistochemical analysis to the main S-phase cyclin, cyclin A, and its regulators p21 CIP1 and p27 KIP1 . Expression of proliferating cell nuclear antigen (PCNA) was used as an additional marker for cells being in either S-or G 2 -phase. In 47% (112/239) of classical Hodgkin's lymphoma cases p21 CIP1 was detected within a mean frequency of 15% positive Hodgkin's and Reed-Sternberg cells per case. Similarly, 47% (116/249) of the cases stained positively for p27 KIP1 with a mean frequency of expression in Hodgkin's and Reed-Sternberg cells of 12%. In contrast, 90% of the cells in all 246 evaluable classical Hodgkin's lymphoma cases were positive for PCNA. In addition, 98% of Hodgkin's and Reed-Sternberg cells in 99% (250/253) of the cases stained strongly positive for cyclin A. These findings further corroborate the hypothesis that Hodgkin and Reed-Sternberg cells exhibit a disturbed cell cycle with an abnormally short or even absent G 1 -phase. In contrast to other tumors, expression of PCNA or cyclin A had no prognostic value for patient survival.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Aberrant expression of cell cycle regulators in Hodgkin and Reed–Sternberg cells of classical Hodgkin's lymphoma

et al. 2005

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“…These H/RS cells harbour clonally rearranged and somatically mutated immunoglobulin genes, indicating that they are derived from germinal centre B cells in most cases (Garcia et al, 2003). On analysing expression of pRb/p105 in Hodgkin's disease samples, a clear difference emerges between cases of nodular lymphocyte predominance, which preserve the relationship between pRb/p105 and Ki67 expression, features similar to reactive lymphadenitis, and classical forms of Hodgkin's disease (nodular sclerosis and mixed cellularity), which display a strong deviation from this pattern.…”

Section: Retinoblastoma Gene Family In Tumours Of Lymphoid Tissuesmentioning

confidence: 99%

“…In particular, the p16-Rb pathway is also presumably inactivated in a large fraction of these samples as the result of p16 INK4a loss (owing to promoter region methylation or deletion) and/or cyclin D overexpression (Garcia et al, 2003).…”

Section: Retinoblastoma Gene Family In Tumours Of Lymphoid Tissuesmentioning

confidence: 99%

Retinoblastoma gene family expression in lymphoid tissues

2006

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It appears more and more clear that retinoblastoma (RB) family of proteins represents key molecules in tumour suppression. This family consists of pRb/p105, p107 and pRb2/p130, which participate in a gene regulatory network that governs the cellular response to antimitogenic signals, and whose deregulation constitutes one of the hallmarks of cancer. Irrespective of their structural and biochemical similarities, RB proteins carry out different functional tasks. The expression of RB gene family in the reactive lymphoid tissues again confirms the different role of each member in cell cycle control and differentiation of normal cells. These different functional properties appear to be maintained in tumours lymphoid tissues, where alterations of the RB/p105 gene appear to be relatively rare. In this review, we will summarize the current knowledge about the role of the RB proteins in reactive and neoplastic lymphoid tissue.

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Current awareness on comparative and functional genomics

2003

Comp Funct Genom

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In order to keep subscribers up‐to‐date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly‐published material on comparative and functional genomics. Each bibliography is divided into 16 sections. 1 Reviews & symposia; 2 General; 3 Large‐scale sequencing and mapping; 4 Genome evolution; 5 Comparative genomics; 6 Gene families and regulons; 7 Pharmacogenomics; 8 Large‐scale mutagenesis programmes; 9 Functional complementation; 10 Transcriptomics; 11 Proteomics; 12 Protein structural genomics; 13 Metabolomics; 14 Genomic approaches to development; 15 Technological advances; 16 Bioinformatics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted

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Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays

Cited by 219 publications

References 46 publications

Aberrant expression of cell cycle regulators in Hodgkin and Reed–Sternberg cells of classical Hodgkin's lymphoma

Aberrant expression of cell cycle regulators in Hodgkin and Reed–Sternberg cells of classical Hodgkin's lymphoma

Retinoblastoma gene family expression in lymphoid tissues

Current awareness on comparative and functional genomics

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