Expression of p53, p21/waf, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas

Kanavaros, Panagiotis; Stefanaki, Kalliopi; Valassiadou, Kalliope; Vlachonikolis, John; Mavromanolakis, M.; Vlychou, Marianna; Kakolyris, S; Gorgoulis, Vassilis G.; Tzardi, Maria; Georgoulias, V.

doi:10.1007/bf02787355

Cited by 51 publications

(64 citation statements)

References 41 publications

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“…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%

“…Our observed low expression levels of p21 CIP1 and p27 KIP1 is in agreement with reports by other authors. 3,23,24 Our data suggest that about 80-90% of Hodgkin and Reed-Sternberg cells are in S-or G 2 -phase, while only about 10-20% are in G 1 -phase. Surprisingly, however, we could only count 57 mitoses in 10 243 cells analyzed.…”

Section: Discussionmentioning

confidence: 60%

“…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%

“…1,2 This mitotic defect could at least partially explain the discrepancy between the high expression of proliferation-associated antigens, such as Ki-67, in Hodgkin and Reed-Sternberg cells and the concomitant lack of successful tumor-cell production. [2][3][4] In addition, Reed-Sternberg cells are polyploid and probably amplify their genome by skipping cytokinesis to repeatedly switch between S-phase and mitosis. 5 We recently demonstrated alterations in the expression of G 1 -phase cyclins in classical Hodgkin's lymphoma, particularly that of cyclin E, 6 the high expression of which led us to conclude that Hodgkin and Reed-Sternberg cells either have a particularly long G 1 -phase or express an abnormally stable cyclin E, which is not degraded in S-phase cells.…”

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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: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

mentioning

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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“…A step of microwave pretreatment was used as described previously (43 1:20), cyclin A (6E6, Novocastra, Newcastle upon Tyne, dilution 1:10), cyclin B1 (7A9, Novocastra, dilution 1:10), p16 (F-12, Santa Cruz Biotechnology, USA, dilution 1:100), and p27 (IB4, Novocastra, dilution 1:20) were applied. Positive control slides were included in all cases.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Low Expression of p27 Protein Combined with Altered p53 and Rb/p16 Expression Status Is Associated with Increased Expression of Cyclin A and Cyclin B1 in Diffuse Large B-Cell Lymphomas

Bai

Vlachonikolis

et al. 2001

Modern Pathology

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The expression of the cyclin-dependent kinase inhibitor (CDKI) p27 protein was investigated in relation to (1) the expression of the cell cycle regulators p53, Rb and p16 and (2) the proliferation profile as determined by the expression of Ki67, cyclin A, and cyclin B1 in 80 cases of de novo diffuse large B-cell lymphomas (DLBCL). P27 expression was low/null in large tumor cells in 58/80 cases and intermediate/high in 22/80 cases. Increased expression of p53 protein was observed in 39/80 cases. Decreased expression of Rb and p16 proteins was mutually exclusive and was observed in 5/80 and 14/80 cases, respectively. The analysis of the p27 expression status (low/null versus intermediate/high) with respect to the p53 and/or Rb/p16 expression status showed that low/null p27 expression was significantly correlated with increased p53 expression (P ‫؍‬ .018) and showed a strong trend for correlation with concurrent increased p53 expression and decreased Rb or p16 expression (P ‫؍‬ .050). These findings suggest a tendency for concurrent alterations of the cell cycle regulators p27, p53, and Rb or p16 in DLBCL, which might result in impaired tumor growth control. Indeed, the analysis of the combined p27/p53/ Rb/p16 expression status with respect to the proliferation profile showed that (1) three alterations in the combined p27/p53/Rb/p16 status (i.e., low/null P27 expression, increased expression of p53, and decreased expression of Rb or p16) were significantly correlated with increased expression of cyclin B1 (P ‫؍‬ .005) and (2) two or three alterations were significantly correlated with increased expression of cyclin A (P ‫؍‬ .014). These findings suggest combined impairment of a complex cell-cycle control network involving the CDK inhibitor p27, the P53 pathway, and the Rb1 pathway, which exerts a cooperative effect resulting in enhanced tumor cell proliferation.

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Combination therapy with irinotecan and protein kinase C inhibitors in malignant glioma

Chen

Fry

et al. 2003

Cancer

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The topoisomerase-I inhibitor irinotecan (CPT-11) is currently used in Phase I/II trials for the treatment of patients with recurrent malignant gliomas. Protein kinase C (PKC) inhibitors such as high-dose tamoxifen and hypericin also have been used in the treatment of malignant gliomas. The current study examined the role of PKC inhibitors as chemosensitizers for CPT-11 and their proposed mechanism of action. Two glioma cell lines (A-172 and U-87) and one primary glioma cell culture (LA-567) were used.Proliferation ( 3 H-thymidine) and cytotoxicity (methylthiotetrazole) studies were performed using CPT-11 (0 -100 M) alone, 7-ethyl-10-hydroxy camptothecin (SN-38) (0 -1000 nM) alone or in the presence of a PKC inhibitor, tamoxifen (10 M), hypericin (10 M), calphositin C (400 nM), or staurosporine (10 nM). The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay was used to determine apoptosis as the mechanism of cytotoxicity; alterations in bcl-2 and bax expression were determined using Western blot analysis. Conversion of CPT-11 to SN-38 by glioma cells was determined using high-performance liquid chromatography

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Expression of p53, p21/waf, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas

Cited by 51 publications

References 41 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

Low Expression of p27 Protein Combined with Altered p53 and Rb/p16 Expression Status Is Associated with Increased Expression of Cyclin A and Cyclin B1 in Diffuse Large B-Cell Lymphomas

Combination therapy with irinotecan and protein kinase C inhibitors in malignant glioma

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