Immunohistochemical Staining for DNA Topoisomerase II in Non-Hodgkin’s Lymphomas

Holden, Joseph A.; Perkins, Sherrie L.; Snow, Gail; Kjeldsberg, Carl R.

doi:10.1093/ajcp/104.1.54

Cited by 65 publications

(43 citation statements)

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“…Meanwhile, topoisomerase II a is highly expressed on aggressive B-cell non-Hodgkin's lymphomas; on the other hand, its expression on T-cell malignancies appears to be generally low, although this conclusion is based on studies with limited samples (Holden et al, 1995;Turley et al, 1997;Korkolopoulou et al, 2001). Our current data with the human T-cell leukaemia cell line Jurkat suggest that the expression of CD26 may be potentially linked to high topoisomerase II a level in selected T-cell malignancies, which are generally aggressive and often difficult to treat at the present time.…”

Section: Discussionmentioning

confidence: 99%

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

et al. 2003

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CD26/dipeptidyl peptidase IV (DPPIV) is a surface antigen with multiple functions, including a role in T-cell activation and the development of certain human cancers. We previously demonstrated that CD26/DPPIV enhanced sensitivity of Jurkat cells to doxorubicin. We now show that expression of CD26/DPPIV enhanced sensitivity of CD26 Jurkat transfectants to G 2 -M arrest mediated by the antineoplastic agent etoposide. The increased sensitivity to etoposide-induced G 2 -M arrest was associated with disruption of cell cycle-related events, including hyperphosphorylation of p34 cdc2 kinase, change in cdc25C expression and phosphorylation, and alteration in cyclin B1 expression. CD26/DPPIV-associated enhancement of doxorubicin and etoposideinduced G 2 -M arrest was also observed in serum-free media, suggesting an effect of CD26 on cell-derived processes rather than serum-derived factors. Importantly, our work elucidated a potential mechanism for the enhanced susceptibility of CD26-expressing Jurkat cells to the topoisomerase II inhibitors by demonstrating that CD26/DPPIV surface expression was associated with increased topoisomerase II a levels and enhanced enzyme activity. Besides being the first to show a functional association between the multifaceted molecule CD26 and the key cellular protein topoisomerase II a, our studies provide additional evidence of a potential role for CD26 in the treatment of selected malignancies.

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Section: Discussionmentioning

confidence: 99%

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

et al. 2003

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“…In each case, nuclei from 500 neoplastic cells from randomly selected fields of the whole section were counted and the Ki-S4 (topo IIa) and Ki-S5 (Ki-67) index was calculated as the percentage of positive nuclei. 26,27 All nuclear staining was counted as topo IIa ( Figures 1 and 2) or Ki-67 positivity. A hematological cell counter (Statitest L10, Ferrari, Berlin, Germany) was used for counting.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…26,27 The aim of this study was to gain more precise information about the topo IIa activity in MCL. We chose cases from two former large studies (1975)(1976)(1977)(1978)(1979)(1980)(1981)(1982)(1983)(1984)(1985) with long follow-up data (up to 15 years) and in the majority of cases (around 90%) without a treatment containing topo inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Topoisomerase IIα expression in mantle cell lymphoma: a marker of cell proliferation and a prognostic factor for clinical outcome

et al. 2004

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Mantle cell lymphoma (MCL) is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3-4 years. Treatment usually consists of combination chemotherapy, often including topoisomerase (topo) inhibitors such as doxorubicin, etoposide and mitoxantrone. Topo IIa is an enzyme that is needed whenever uncoiling of DNA is necessary during the cell cycle. The enzyme is a marker of cell proliferation. We analyzed the expression of topo IIa in relation to Ki-67 and the clinical outcome in patients with MCL. Biopsy specimens from 95 untreated patients enrolled in two multicenter trials (1975)(1976)(1977)(1978)(1979)(1980)(1981)(1982)(1983)(1984)(1985) were investigated immunohistochemically with monoclonal antibodies against topo IIa (Ki-S4) and Ki-67 (Ki-S5). Patients with low (0-10%) topo IIa expression had a median overall survival time of 49.0 months, compared to 17.0 months for patients with high (more than 10%) topo IIa expression. The Kaplan-Meier analysis showed a significant difference in the overall survival time related to the percentage of topo IIa (Po0.001) and Ki-67 (Po0.001) positive tumor cells. Multivariate Cox regression analysis revealed the expression of topo IIa as the most important prognostic factor (Po0.001) in MCL superior to the international prognostic index (IPI), the Ki-67 index and other clinical characteristics.

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“…Topoisomerase II ␣ (topo II ␣) is also a proliferation marker (12)(13)(14) and functions to prevent nondisjunction and chromosome breakage in mitosis (15,16). Topo II ␣ has been used recently to assess proliferative activity in neoplasms (12)(13)(14).…”

Section: Mod Pathol 2000;13(9):1014 -1019mentioning

confidence: 99%

“…Topo II ␣ is associated with cell proliferation (12)(13)(14) and functions in mitoses to prevent nondisjunction and chromosome breakage (15,16). Recent studies have indicated that topo II ␣ may have diagnostic or prognostic significance in a variety of tumors including gliomas (25), salivary gland adenoid cystic carcinomas (26), esophageal squamous cell carcinomas (27), gastric and colonic carcinomas (28), adrenal carcinomas (29), and thyroid carcinomas (30).…”

Section: Discusssionmentioning

confidence: 99%

p27kip1 Expression Distinguishes Papillary Hyperplasia in Graves' Disease from Papillary Thyroid Carcinoma

et al. 2000

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In most cases, the histopathologic and cytologic distinction between Graves' disease and papillary thyroid carcinoma is relatively easy, but on occasion Graves' disease may simulate a thyroid papillary carcinoma. For example, papillary fronds with fibrovascular cores may be present in both Graves' disease and papillary carcinoma. p27 kip1 (p27) is a cyclin-dependent kinase inhibitory protein that has been shown to be an independent prognostic factor in a variety of human tumors. Our previous studies of p27 expression in hyperplastic and neoplastic endocrine lesions showed that the level of p27 was quite different in these two conditions. To determine if this distinction could also be made between Graves' disease and papillary carcinoma, we analyzed expression of p27 and other cell cycle proteins in a series of cases of Graves' disease with papillary hyperplasia and a series of papillary thyroid carcinomas. Formalin-fixed paraffin-embedded tissues from 61 randomly selected patients with thyroid disease, including 29 cases of Graves' disease with papillary architectural features and 32 cases of papillary carcinoma, were analyzed for expression of p27, Ki-67, and DNA topoisomerase II ␣ (topo II ␣) by immunostaining. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index (LI) plus or minus the standard error of the mean. The papillary hyperplasia of Graves' disease had a p27 LI of 68.2 ؎ 3.1 (range, 24 to 88), whereas papillary carcinomas had a LI of 25.6 ؎ 2.5 (range, 12 to 70) (P < .0001). No significant differences in Ki-67 or topo II ␣ expression were identified between papillary hyperplasia in Graves' disease and papillary carcinoma. These results indicate that p27 protein expression is significantly higher in papil-

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Immunohistochemical Staining for DNA Topoisomerase II in Non-Hodgkin’s Lymphomas

Cited by 65 publications

References 0 publications

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

Topoisomerase IIα expression in mantle cell lymphoma: a marker of cell proliferation and a prognostic factor for clinical outcome

p27kip1 Expression Distinguishes Papillary Hyperplasia in Graves' Disease from Papillary Thyroid Carcinoma

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