Immunohistochemical staining of DNA topoisomerase IIα in human gliomas

Taniguchi, Katsumi; Wakabayashi, Toshihiko; Yoshida, Tomoo; Mizuno, Masaaki; Yoshikawa, Kazuhiro; Kikuchi, Akihiko; Nakashima, Naoki; Yoshida, Jun

doi:10.3171/jns.1999.91.3.0477

Cited by 50 publications

(32 citation statements)

References 22 publications

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“…In contrast to MIB-1, which reacts with all phases of the cell cycle except G 0 , TII␣ expression can also be detected in some parts of the G 0 phase. 10 This observation is in line with a recent hypothesis that in cancer cells, overexpression of TII␣ might reflect not only the proliferative activity of these cells but also qualitative alterations in TII␣ expression caused by malignant transformation. In general support of this notion, TII␣ expression has been found to be closely related to other indicators of high malignant potential.…”

Section: Relationship Between Tii␣ and Other Prognostic Factorssupporting

confidence: 79%

“…Expression of this protein has been suggested to provide prognostic information in adult malignant gliomas. 9,10 In addition, TII␣ has been related to a certain form of multidrug resistance to a number of anticancer agents in these neoplasms. 11 Accordingly, assessing the expression of this enzyme in MNBGs may potentially also provide information on an immediate molecular target of chemotherapy.…”

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confidence: 99%

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DNA topoisomerase IIα predicts progression‐free and overall survival in pediatric malignant non‐brainstem gliomas

Bredel

Pollack

Hamilton

et al. 2002

Intl Journal of Cancer

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Malignant non-brainstem glioma (MNBG) is a rare pediatric brain tumor. The prognosis for children harboring this lesion remains largely unpredictable. Assessment of histologic features alone only provides a marginal insight into the biologic behavior of these lesions. Hence, the identification of novel molecular markers capable of characterizing these lesions more accurately with respect to their biologic aggressiveness is definitely needed. Our current study examined the expression of nuclear DNA topoisomerase II␣ (TII␣), a novel marker of cell cycle turnover and a determinant of tumor cell resistance to chemotherapy, in a series of 17 archival pediatric MNBGs. TII␣ expression was found to extend over a wide range in the study cohort (3.9 -69.1%). A cutoff labeling index of 12% was found to define 2 prognostic subgroups (TII␣ <12 vs. >12) with profoundly different 5-year progression-free survival (60% vs. 8%; p ‫؍‬ 0.0108, logrank test) and overall survival (100% vs. 8%; p ‫؍‬ 0.0038) rates. TII␣ expression was significantly linked to MIB-1 antibody labeling of the Ki-67 nuclear antigen (R ‫؍‬ 0.919, p < 0.001). A high TII␣ labeling index remained associated with short progression-free survival (p ‫؍‬ 0.022) and overall survival (p ‫؍‬ 0.022) in multivariate analysis (Cox regression). In conclusion, considering that TII␣ expression was not related to histopathologic grade, biological characteristics as assessed by TII␣ labeling may complement the information obtained by tumor morphology as a means of improving the accuracy of patient prognosis prediction.

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Section: Relationship Between Tii␣ and Other Prognostic Factorssupporting

confidence: 79%

mentioning

confidence: 99%

DNA topoisomerase IIα predicts progression‐free and overall survival in pediatric malignant non‐brainstem gliomas

Bredel

Pollack

Hamilton

et al. 2002

Intl Journal of Cancer

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“…mutations) are consistent with increased transcription of topo II· mRNA and a concomitant augmentation of its protein levels that might entail a growth advantage. Moreover, in malignant cells, overexpression of the topo II· protein may reflect not only the proliferative advantage of these cells, but also qualitative alterations caused by malignant transformation and dedifferentiation [1]. Actually, in a recent study, treatment of the hepatoma cell line Hep3B with retinoids (which can induce cell differentiation) seemed to have a direct effect on the topo II· gene promoter since it markedly reduced both the steady-state level of the mRNA and the transcription rate of the topo II· gene [23].…”

Section: Discussionmentioning

confidence: 99%

“…The enzyme performs these functions by cleaving and opening one DNA duplex, passing the second duplex through the opening and then resealing the break [1]. Dysregulation or qualitative alterations of the enzyme's isoform, topo II·, in the cell cycle have been reported in both normal tissues and various Nakopoulou/Lazaris/Kavantzas/ Alexandrou/Athanassiadou/Keramopoulos/ Davaris human neoplasms [1][2][3][4]. In addition to cellular proliferation, the sensitivity or resistance of a malignant cell to several antitumor drugs known as 'topo II poisons' is quantitatively dependent on the cellular content of topo II.…”

Section: Introductionmentioning

confidence: 99%

DNA Topoisomerase II-Alpha Immunoreactivity as a Marker of Tumor Aggressiveness in Invasive Breast Cancer

Nakopoulou¹,

Lazaris²,

Kavantzas³

et al. 2000

Pathobiology

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Objective: The nuclear enzyme DNA topoisomerase (topo) II breaks and rejoins DNA strands; its isoform topo IIα is associated with active cell proliferation of mammalian cells. The aim of this study was to examine the relationship between the expression of topo IIα and biological behavior markers in breast cancer. Methods: Formalin-fixed, paraffin-embedded tissue from 88 samples of infiltrating breast cancer was immunohistochemically stained for topo IIα. For each case, a topo IIα index was determined by image analysis. Similar indexes were available for Ki-67 protein, a known cell proliferation marker, and p53, bcl-2 and c-erbB-2 oncoproteins. Each case had been staged and graded and the patients had been followed up for a mean period of 61.62 months. Results: Elevated topo IIα immunopositivity (in >10% of malignant nuclei) was detected in 22 tumors, and this immunostatus was statistically associated with poor nuclear differentiation, absence of steroid hormone receptors, high Ki-67 immunoexpression, p53 protein accumulation and c-erbB-2 protein overexpression. Topo IIα expression was not linked with disease extent (stage or lymph node status). Neither proliferation marker (topo IIα or Ki-67) had any significant influence on the patients’ recurrence-free survival. Conclusion: From the above results, we conclude that topo IIα overexpression appears to be linked with cellular dedifferentiation and potentially aggressive tumor phenotype in invasive breast cancer.

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“…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). Among thyroid neoplasms, topo II ␣ is more frequently expressed in tumors with more aggressive clinical behavior such as anaplastic carcinomas, tall cell variant of papillary carcinomas, follicular and Hurthle cell carcinomas, and medullary 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 of DNA topoisomerase IIα in human gliomas

Abstract: Immunostaining for Topo IIalpha represents a useful alternative to MIB-1 as a proliferative index in human gliomas.

Cited by 50 publications

References 22 publications

DNA topoisomerase IIα predicts progression‐free and overall survival in pediatric malignant non‐brainstem gliomas

DNA topoisomerase IIα predicts progression‐free and overall survival in pediatric malignant non‐brainstem gliomas

DNA Topoisomerase II-Alpha Immunoreactivity as a Marker of Tumor Aggressiveness in Invasive Breast Cancer

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

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