Proliferating cell nuclear antigen in breast lesions: Correlation of c-erbB-2 oncoprotein and EGF receptor and its clinicopathological significance in breast cancer

Shrestha, Pragya; Yamada, Kazuto; Wada, Tetsuyuki; Maeda, S.; Watatani, Masahiro; Yasutomi, Masayuki; Takagi, Hitoshi; Mori, Masahiko

doi:10.1007/bf01611175

Cited by 37 publications

(18 citation statements)

References 41 publications

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“…In this paper, we demonstrate that all three features are affected by Her2/neu overexpression. Several clinical reports indicate that increased tumor cell proliferation is associated with overexpression of Her2 [13][14][15][16]. Her2 overexpression can also result in increased blood vessel growth as a result of its influence on VEGF expression [18,19].…”

Section: Discussionmentioning

confidence: 99%

“…Low vascular density and increased O 2 consumption are affected by Her2/neu expression in tumors. Laboratory studies have shown that Her2 overexpression increases breast tumor cell proliferation which should increase oxygen consumption rates [13][14][15][16]. However, Her2 overexpression can also drive angiogenesis by increasing expression of the proangiogenic cytokine vascular endothelial growth factor (VEGF), independent of hypoxic upregulation [17].…”

Section: Introductionmentioning

confidence: 99%

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Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors

Hardee

Eapen²,

Rabbani

et al. 2008

Cancer Chemother Pharmacol

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Purpose Tumor hypoxia reduces the efficacy of radiation and chemotherapy as well as altering gene expression that promotes cell survival and metastasis. The growth factor receptor, Her2/neu, is overexpressed in 25-30% of breast tumors. Tumors that are Her2 + may have an altered state of oxygenation, relative to Her2 -tumors, due to differences in tumor growth rate and angiogenesis. Methods Her2 blockade was accomplished using an antibody to the receptor (trastuzumab; Herceptin). This study examined the effects of Her2 blockade on tumor angiogenesis, vascular architecture, and hypoxia in Her2 + and Her2 -MCF7 xenograft tumors.Results Treatment with trastuzumab in Her2 + tumors significantly improved tumor oxygenation, increased microvessel density, and improved vascular architecture compared with the control-treated Her2 + tumors. The Her2 + xenografts treated with trastuzumab also demonstrated decreased proliferation indices when compared with control-treated xenografts. These results indicate that Her2 blockade can improve tumor oxygenation by decreasing oxygen consumption (reducing tumor cell proliferation and inducing necrosis) and increasing oxygen delivery (vascular density and architecture). Conclusions These results support the use of trastuzumab as an adjunct in the treatment of breast tumors with chemotherapy or radiotherapy, as improvements in tumor oxygenation should translate into improved treatment response.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors

Hardee

Eapen²,

Rabbani

et al. 2008

Cancer Chemother Pharmacol

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“…Moreover, overexpressions of c-erbB-2 [20,33,34] and p53 [9,15,28] oncoproteins were suggested to be associated with poor prognosis of breast carcinoma. However, other investigations indicate the lack of evidence for prognostic significance of overexpressions of c-erbB-2 [35] and p53 [5,6] oncoproteins.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Factors and Proliferative Activities in Breast Cancer. A Comparative Study between Recurrent and Non-Recurrent Cases of Human Breast Carcinomas.

Imamura

Ishida

Horita

et al. 1997

Acta Histochem. Cytochem

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“…2,7,25,36,42 Some researchers have noted the value of these nuclear antigens in the prediction of disease-free survival and overall survival as independent prognostic factors in multivariate analyses. 38,41,43 Other authors have reported inconsistent results.…”

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confidence: 99%

Immunohistochemical Detection of Ki-67 and PCNA in Canine Mammary Tumors: Relationship to Clinical and Pathologic Variables

et al. 1998

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The objectives of this study were to measure the proliferation indices in canine mammary tumors using immunohistochemical detection of Ki-67 and proliferating cell nuclear antigen (PCNA), to determine the relationship of these antigens to clinical and pathologic variables, and to investigate the usefulness of these antigens as prognostic indicators. Ninety-six female dogs with 115 primary nonmetastasized spontaneous mammary tumors and dysplasias were included in the study. Immunostaining was performed using MIB-1 and PC10 monoclonal antibodies against Ki-67 and PCNA, respectively. Ki-67 and PCNA proliferation indices were determined. Dogs were followed for 18 months, with clinical examinations every 3-4 months. There was a significant correlation between Ki-67 and PCNA indices in the dogs with dysplasias and benign tumors but not in the dogs with malignant tumors. The clinical stage at first presentation was related to the proliferative index measured with Ki-67 but not to that measured with PCNA. Proliferation indices were significantly lower in the nonmalignant tumors and dysplasias than in the malignant tumors. In malignant tumors, the PCNA index had a positive correlation with the histologic malignant grade and the nuclear grade. High index values of Ki-67 were positively correlated with metastasis, death from neoplasia, low disease-free survival rates, and low overall survival rates. PCNA displayed no significant association with these variables. Multivariate analyses concerning metastasis, disease-free survival, and overall survival revealed that the Ki-67 index had prognostic value.

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Proliferating cell nuclear antigen in breast lesions: Correlation of c-erbB-2 oncoprotein and EGF receptor and its clinicopathological significance in breast cancer

Cited by 37 publications

References 41 publications

Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors

Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors

Prognostic Factors and Proliferative Activities in Breast Cancer. A Comparative Study between Recurrent and Non-Recurrent Cases of Human Breast Carcinomas.

Immunohistochemical Detection of Ki-67 and PCNA in Canine Mammary Tumors: Relationship to Clinical and Pathologic Variables

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