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BCL-2, topoisomerase IIα, microvessel density and prognosis of early advanced breast cancer patients after adjuvant anthracycline-based chemotherapy.

Biesaga B, Niemiec J, Ziobro M - J. Cancer Res. Clin. Oncol. (2014)

Bottom Line: The aim of this retrospective study was to investigate the effect of B cell lymphoma 2 (BCL-2) expression on disease-free survival (DFS) in 172 early breast cancer (BC) patients treated with anthracycline-based adjuvant chemotherapy.In multivariate analysis, BCL-2, TOPOIIα and MVD were independent parameters indicating patient prognosis.Combination of three parameters: BCL-2 positivity, low topoisomerase IIα expression and high MVD, allows to identify subgroup of BC patients with very good prognosis after adjuvant anthracycline-based chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Radiobiology, Centre of Oncology, ul. Garncarska 11, 31-115, Kraków, Poland, z5biesag@cyfronet.pl.

ABSTRACT

Purpose: The aim of this retrospective study was to investigate the effect of B cell lymphoma 2 (BCL-2) expression on disease-free survival (DFS) in 172 early breast cancer (BC) patients treated with anthracycline-based adjuvant chemotherapy. We have reanalysed follow-up data in these patient groups, and therefore, the relation between DFS and other tumour biological features [expression of oestrogen (ER) and progesterone (PgR) receptors, cytokeratin 5/6 (CK5/6), HER2, topoisomerase IIα (TOPOIIα), Ki-67, P53 and microvessel density (MVD)] studied previously (Biesaga et al. in Breast 20(4):338-350, 2011, doi: 10.1016/j.breast.2011.03.002 , Pathol Oncol Res 18(4): 949-960, 2012, doi: 10.1007/s12253-012-9525-9 ) was also investigated.

Method: Tumour biological features were assessed immunohistochemically on paraffin-embedded sections obtained before treatment from 172 women with BC in stage T1-T2, N1-N2, M0.

Results: In univariate analysis, longer DFS was found for patients having tumours with BCL-2 positivity (P = 0.005), low grade (P = 0.001), ER (P = 0.017) and PgR (P = 0.045) positivity, CK5/6 negativity (P = 0.021), low TOPOIIα expression (P = 0.003) and high MVD (P = 0.000). In multivariate analysis, BCL-2, TOPOIIα and MVD were independent parameters indicating patient prognosis. All patients (n = 18) characterized by tumour BCL-2 positivity, low TOPOIIα expression and high MVD survived 80 months without any evidence of cancer disease, whereas DFS for all other patients was significantly (P = 0.022) lower (76.5 %).

Conclusion: Combination of three parameters: BCL-2 positivity, low topoisomerase IIα expression and high MVD, allows to identify subgroup of BC patients with very good prognosis after adjuvant anthracycline-based chemotherapy.

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Representative images of BCL-2 immunohistochemical staining in breast cancer tissue and correlation between BCL-2 immunoexpression and other biological features studied. a Negative BCL-2 staining (class 0—no BCL-2 expression). b Heterogeneous BCL-2 immunostaining within tumour area (class 1—BCL-2 expression). c Intense BCL-2 staining in all tumour cells (class 2—BCL-2 overexpression), ×200 magnification. BCL-2 overexpression is correlated with d low proliferation rate assessed by Ki-67 labelling index (Ki-67LI), e low P53 level expressed as P53 labelling index (P53LI) (Kruskal–Wallis test)
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Fig1: Representative images of BCL-2 immunohistochemical staining in breast cancer tissue and correlation between BCL-2 immunoexpression and other biological features studied. a Negative BCL-2 staining (class 0—no BCL-2 expression). b Heterogeneous BCL-2 immunostaining within tumour area (class 1—BCL-2 expression). c Intense BCL-2 staining in all tumour cells (class 2—BCL-2 overexpression), ×200 magnification. BCL-2 overexpression is correlated with d low proliferation rate assessed by Ki-67 labelling index (Ki-67LI), e low P53 level expressed as P53 labelling index (P53LI) (Kruskal–Wallis test)

Mentions: Samples were analysed using Olympus microscope at 400× magnification. BCL-2 expression was scored according to classification presented by Treré et al. (2007), because based on it, they found significant relation between BCL-2 expression assessed by IHC and its mRNA level. According to this scale, three classes of BCL-2 expression were identified: 0—lack of immunostaining (no BCL-2 expression), 1—heterogeneous staining within tumour area, regardless of the intensity (BCL-2 expression) and 2—intense staining in all tumour cells (BCL-2 overexpression) (Fig. 1a–c).Fig. 1


BCL-2, topoisomerase IIα, microvessel density and prognosis of early advanced breast cancer patients after adjuvant anthracycline-based chemotherapy.

Biesaga B, Niemiec J, Ziobro M - J. Cancer Res. Clin. Oncol. (2014)

Representative images of BCL-2 immunohistochemical staining in breast cancer tissue and correlation between BCL-2 immunoexpression and other biological features studied. a Negative BCL-2 staining (class 0—no BCL-2 expression). b Heterogeneous BCL-2 immunostaining within tumour area (class 1—BCL-2 expression). c Intense BCL-2 staining in all tumour cells (class 2—BCL-2 overexpression), ×200 magnification. BCL-2 overexpression is correlated with d low proliferation rate assessed by Ki-67 labelling index (Ki-67LI), e low P53 level expressed as P53 labelling index (P53LI) (Kruskal–Wallis test)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4228164&req=5

Fig1: Representative images of BCL-2 immunohistochemical staining in breast cancer tissue and correlation between BCL-2 immunoexpression and other biological features studied. a Negative BCL-2 staining (class 0—no BCL-2 expression). b Heterogeneous BCL-2 immunostaining within tumour area (class 1—BCL-2 expression). c Intense BCL-2 staining in all tumour cells (class 2—BCL-2 overexpression), ×200 magnification. BCL-2 overexpression is correlated with d low proliferation rate assessed by Ki-67 labelling index (Ki-67LI), e low P53 level expressed as P53 labelling index (P53LI) (Kruskal–Wallis test)
Mentions: Samples were analysed using Olympus microscope at 400× magnification. BCL-2 expression was scored according to classification presented by Treré et al. (2007), because based on it, they found significant relation between BCL-2 expression assessed by IHC and its mRNA level. According to this scale, three classes of BCL-2 expression were identified: 0—lack of immunostaining (no BCL-2 expression), 1—heterogeneous staining within tumour area, regardless of the intensity (BCL-2 expression) and 2—intense staining in all tumour cells (BCL-2 overexpression) (Fig. 1a–c).Fig. 1

Bottom Line: The aim of this retrospective study was to investigate the effect of B cell lymphoma 2 (BCL-2) expression on disease-free survival (DFS) in 172 early breast cancer (BC) patients treated with anthracycline-based adjuvant chemotherapy.In multivariate analysis, BCL-2, TOPOIIα and MVD were independent parameters indicating patient prognosis.Combination of three parameters: BCL-2 positivity, low topoisomerase IIα expression and high MVD, allows to identify subgroup of BC patients with very good prognosis after adjuvant anthracycline-based chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Radiobiology, Centre of Oncology, ul. Garncarska 11, 31-115, Kraków, Poland, z5biesag@cyfronet.pl.

ABSTRACT

Purpose: The aim of this retrospective study was to investigate the effect of B cell lymphoma 2 (BCL-2) expression on disease-free survival (DFS) in 172 early breast cancer (BC) patients treated with anthracycline-based adjuvant chemotherapy. We have reanalysed follow-up data in these patient groups, and therefore, the relation between DFS and other tumour biological features [expression of oestrogen (ER) and progesterone (PgR) receptors, cytokeratin 5/6 (CK5/6), HER2, topoisomerase IIα (TOPOIIα), Ki-67, P53 and microvessel density (MVD)] studied previously (Biesaga et al. in Breast 20(4):338-350, 2011, doi: 10.1016/j.breast.2011.03.002 , Pathol Oncol Res 18(4): 949-960, 2012, doi: 10.1007/s12253-012-9525-9 ) was also investigated.

Method: Tumour biological features were assessed immunohistochemically on paraffin-embedded sections obtained before treatment from 172 women with BC in stage T1-T2, N1-N2, M0.

Results: In univariate analysis, longer DFS was found for patients having tumours with BCL-2 positivity (P = 0.005), low grade (P = 0.001), ER (P = 0.017) and PgR (P = 0.045) positivity, CK5/6 negativity (P = 0.021), low TOPOIIα expression (P = 0.003) and high MVD (P = 0.000). In multivariate analysis, BCL-2, TOPOIIα and MVD were independent parameters indicating patient prognosis. All patients (n = 18) characterized by tumour BCL-2 positivity, low TOPOIIα expression and high MVD survived 80 months without any evidence of cancer disease, whereas DFS for all other patients was significantly (P = 0.022) lower (76.5 %).

Conclusion: Combination of three parameters: BCL-2 positivity, low topoisomerase IIα expression and high MVD, allows to identify subgroup of BC patients with very good prognosis after adjuvant anthracycline-based chemotherapy.

Show MeSH
Related in: MedlinePlus