Correlation between p53, c-erbB-2, and topoisomerase II? expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas: prognostic implications

Rudolph, Pierre; Olsson, Håkan; Bonatz, G.; Ratjen, Virgo; Bolte, Hendrik; Baldetorp, Bo; Fernö, Mårten; Parwaresch, Reza; Alm, Per

doi:10.1002/(sici)1096-9896(199901)187:2<207::aid-path223>3.0.co;2-u

Cited by 113 publications

(57 citation statements)

References 47 publications

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“…Contrary to previous results from our group (Rudolph et al, 1999a) and others (Jarvinen et al, 1996(Jarvinen et al, , 1998Rudolph et al, 1999b), we failed to observe a significant positive correlation between Topo IIa expression and Her-2/neu-overexpression in this series. Approximately 50% of the Her-2/neu overexpressing tumours in our series contained high levels of Topo IIa, whereas in the remaining 50%, Topo IIa was low (Table 1).…”

Section: Discussioncontrasting

confidence: 99%

DNA topoisomerase IIα expression and the response to primary chemotherapy in breast cancer

MacGrogan

Rudolph²,

Mascarel

et al. 2003

Br J Cancer

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The a isoform of Topoisomerase IIa (Topo IIa) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIa expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T 2 43 cm and T 3 N 0 -1 M 0 breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo IIa. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (415%) was associated with tumour regression under chemotherapy (OR ¼ 2.88, CI: 1.3 -6.4, P ¼ 0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR ¼ 3.34, CI: 1.41 -7.93, P ¼ 0.006), together with tumour size of less than 40 mm (OR ¼ 3.82, CI: 1.58 -9.25, P ¼ 0.002) and negative oestrogen receptor (ER) status (OR ¼ 3.35, CI: 1.43 -7.86, P ¼ 0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/neu. Our clinical results confirm in vitro data on the relationship between Topo IIa expression and tumour chemosensitivity and thus may have important practical implications.

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Section: Discussioncontrasting

confidence: 99%

DNA topoisomerase IIα expression and the response to primary chemotherapy in breast cancer

MacGrogan

Rudolph²,

Mascarel

et al. 2003

Br J Cancer

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“…The prognostic value of topo IIa expression in other malignancies (breast carcinomas, non-Hodgkin's lymphomas, Hodgkin's disease) has been investigated before. [23][24][25][26] High topo Figure 3 Overall survival time of 95 patients with MCL and different IPI scores (log-rank test, univariate analysis).…”

Section: Resultsmentioning

confidence: 99%

“…22 The cell cycle-dependent expression of topo IIa indicated by Ki-S4 in archival tissue has been used for prognostic evaluation in patients with other malignancies. [23][24][25] The topo IIa enzyme is a cell proliferation marker but also a target for many chemotherapeutic agents. The treatment of MCL usually consists of combination chemotherapy.…”

Section: Introductionmentioning

confidence: 90%

“…The detection of the reactive epitopes in fixed material required prior antigen retrieval. This was achieved for anti-topo IIa (Ki-S4, undiluted cell culture supernatant, Department of Hematopathology, University of Kiel, Germany) [22][23][24] and anti-Ki-67 (Ki-S5, undiluted cell culture supernatant, Department of Hematopathology, University of Kiel, Germany). 5,35 by boiling the sections immersed in 0.01 M citric acid, pH 6.0, for 2 min 30 s in a pressure cooker.…”

Section: Immunohistochemistrymentioning

confidence: 99%

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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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“…Intranuclear levels are therefore cell-cycle and proliferation dependent, with overexpression reported in a number of human malignancies (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Tissue sections from a number of these tumors show parallel immunoreactivity for topo II␣ and the proliferation marker Ki-67.…”

mentioning

confidence: 99%

DNA Topoisomerase IIα in Multiple Myeloma: A Marker of Cell Proliferation and Not Drug Resistance

et al. 2001

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DNA topoisomerase II␣ (topo II␣) is the target for a number of antineoplastic agents. Down-regulation of this enzyme is one form of drug resistance. Topo II␣ is also involved in DNA replication and transcription and serves as an indicator of proliferation rate in many human malignancies. This study examines whether topo II␣ is one of the mechanisms of chemoresistance commonly observed in multiple myeloma (MM) or alternatively, whether topo II␣ is associated with tumor cell proliferation. Bone marrow (BM) biopsy sections from 72 cases of MM, stratified according to proliferative activity (bromodeoxyuridine uptake), were immunostained for topo II␣. Immunoreactivity with an additional marker of drug resistance, glutathione-Stransferase , and the proliferation marker Ki-67 were also examined. Topo II␣ was expressed in 26 (36%) cases and correlated strongly with proliferative activity (P < .001). A role for drug resistance could not be supported, given this strong relationship with proliferation and the finding that glutathione-S-transferase expression in 57 (78%) cases was independent of topo II␣ immunoreactivity. Topo II␣ was identified in 91 to 100% of highly proliferative tumors, as evaluated by bromodeoxyuridine uptake or Ki-67 reactivity, respectively. Proliferation also correlated with the histologic grade of the MM. Therefore, topo II␣ immunoreactivity is primarily a marker of cell proliferation in MM and as such is likely to have prognostic significance. Highly proliferative tumors are most likely to be sensitive to chemotherapeutic protocols using anti-topo II␣ agents.

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Correlation between p53, c-erbB-2, and topoisomerase II? expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas: prognostic implications

Cited by 113 publications

References 47 publications

DNA topoisomerase IIα expression and the response to primary chemotherapy in breast cancer

DNA topoisomerase IIα expression and the response to primary chemotherapy in breast cancer

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

DNA Topoisomerase IIα in Multiple Myeloma: A Marker of Cell Proliferation and Not Drug Resistance

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