Limits...
DNA topoisomerase IIalpha expression and the response toprimary chemotherapy in breast cancer.

MacGrogan G, Rudolph P, Mascarel Id Id, Mauriac L, Durand M, Avril A, Dilhuydy JM, Robert J, Mathoulin-Pélissier S, Picot V, Floquet A, Sierankowski G, Coindre JM - Br. J. Cancer (2003)

Bottom Line: The alpha isoform of Topoisomerase IIalpha (Topo IIalpha) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines.To verify this effect in vivo, we selected 125 patients presenting with T(2)>3 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.Ki-S7 positivity ranged from 0 to 50% (median, 15%).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Institut Bergonié, 229 Cours de l'Argonne, 33076 Bordeaux cedex France. macgrogan@bergonie.org

ABSTRACT
The alpha isoform of Topoisomerase IIalpha (Topo IIalpha) 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 IIalpha expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T(2)>3 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 IIalpha. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3-6.4, P=0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41-7.93, P=0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58-9.25, P=0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43-7.86, P=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 IIalpha expression and tumour chemosensitivity and thus may have important practical implications.

Show MeSH

Related in: MedlinePlus

Nuclear immunostaining (Topo IIα) of 25% cells in a Holland's bouin-fixed paraffin-embedded microbiopsy of an invasive ductal carcinoma NOS using monoclonal antibody Ki-S7 specific for topoisomerase IIα (A). Haematoxylin eosin saffron stain of the same case (B). Scale bar=50 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2376904&req=5

fig1: Nuclear immunostaining (Topo IIα) of 25% cells in a Holland's bouin-fixed paraffin-embedded microbiopsy of an invasive ductal carcinoma NOS using monoclonal antibody Ki-S7 specific for topoisomerase IIα (A). Haematoxylin eosin saffron stain of the same case (B). Scale bar=50 μm.

Mentions: All slides were read by one of the authors (GMG) who was blinded to the clinical results. Only unequivocal nuclear staining of invasive tumour cells was scored as positive (Figure 1Figure 1


DNA topoisomerase IIalpha expression and the response toprimary chemotherapy in breast cancer.

MacGrogan G, Rudolph P, Mascarel Id Id, Mauriac L, Durand M, Avril A, Dilhuydy JM, Robert J, Mathoulin-Pélissier S, Picot V, Floquet A, Sierankowski G, Coindre JM - Br. J. Cancer (2003)

Nuclear immunostaining (Topo IIα) of 25% cells in a Holland's bouin-fixed paraffin-embedded microbiopsy of an invasive ductal carcinoma NOS using monoclonal antibody Ki-S7 specific for topoisomerase IIα (A). Haematoxylin eosin saffron stain of the same case (B). Scale bar=50 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376904&req=5

fig1: Nuclear immunostaining (Topo IIα) of 25% cells in a Holland's bouin-fixed paraffin-embedded microbiopsy of an invasive ductal carcinoma NOS using monoclonal antibody Ki-S7 specific for topoisomerase IIα (A). Haematoxylin eosin saffron stain of the same case (B). Scale bar=50 μm.
Mentions: All slides were read by one of the authors (GMG) who was blinded to the clinical results. Only unequivocal nuclear staining of invasive tumour cells was scored as positive (Figure 1Figure 1

Bottom Line: The alpha isoform of Topoisomerase IIalpha (Topo IIalpha) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines.To verify this effect in vivo, we selected 125 patients presenting with T(2)>3 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.Ki-S7 positivity ranged from 0 to 50% (median, 15%).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Institut Bergonié, 229 Cours de l'Argonne, 33076 Bordeaux cedex France. macgrogan@bergonie.org

ABSTRACT
The alpha isoform of Topoisomerase IIalpha (Topo IIalpha) 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 IIalpha expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T(2)>3 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 IIalpha. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3-6.4, P=0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41-7.93, P=0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58-9.25, P=0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43-7.86, P=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 IIalpha expression and tumour chemosensitivity and thus may have important practical implications.

Show MeSH
Related in: MedlinePlus