Prognostic value of gene expression of p63 by microarray analysis in estrogen receptor positive and negative breast cancer

566 Background: The protein 63 (p63) represents a member of the p53 family (p53/p63/p73) located on chromosome 3q27. This gene family seems to play an important role in carcinogenesis and its members may act as oncogenes or tumor suppressor genes. P63 is overexpressed in many different tumors like head and neck cancer, lung cancers, uterine tumors and breast cancer, and has been associated with poor prognosis in some studies. P63 was found to be overexpressed in a subset of highly aggressive breast cancers that represent a basal and myoepithelial phenotype and have a poor clinical outcome. This protein seems to be a specific myoepithelial cell marker in normal breast tissue and might represent a prognostic factor in breast cancer. Methods: Large scale analysis was performed using Affymetrix microarray data from n=1581 breast cancer patients to evaluate p63 expression. Results: P63 expression showed a strong correlation with patient's age (χ2-test, p < 0.001), tumor size (p < 0.003), proliferation rate (p < 0.001), Topo2α expression (p = 0.001) and estrogen receptor expression (p = 0.017). Survival analysis of all patients with available follow up data (n = 1263) showed a significant difference due to high and low p63 expression (log rank p < 0.001). Patients with a low p63 expression had the worst prognosis. In univariate Cox regression analysis p63 showed a hazard ratio (HR) of 1.61 (95% CI 1.31–2.00, p < 0.001) for disease free survival. This prognostic impact remained significant when samples were stratified by estrogen receptor status. High expression of p63 was significantly associated with longer OS in both ER negative (n = 334, log rank p = 0.022) and ER positive (n = 929, log rank p < 0,001) breast cancer. The prognostic impact of p63 expression was independent of Ki67 expression (p = 0.011 and p = 0.001 for high and low Ki67, respectively). Moreover a worse prognosis of low p63 expressing tumors was found in both subgroups of ErbB2 positive tumors (p < 0.001) and ErbB2 negative tumors (p < 0.001). Conclusions: P63 expression is a prognostic factor in both ER positive and negative breast cancer and could be helpful for risk assessment in breast cancer patients. No significant financial relationships to disclose.

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Ki-67 Expression is a Significant Prognostic Factor Only When Progesterone Receptor Expression is Low in Estrogen Receptor-Positive and HER2-Negative Early Breast Cancer

Journal of Oncology ◽

10.1155/2019/7386734 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Young-Joon Kang ◽

Han-Byoel Lee ◽

Yun Gyoung Kim ◽

JaiHong Han ◽

Yumi Kim ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Prognostic Factor ◽

Progesterone Receptor ◽

Cancer Patients ◽

Early Breast Cancer ◽

Receptor Expression ◽

Breast Cancer Patients ◽

Ki 67 ◽

End Point

Objective. While the value of Ki-67 has been recognized in breast cancer, controversy also exists. The goal of this study is to show the prognostic value of Ki-67 according to progesterone receptor (PgR) expression in patients who have estrogen receptor- (ER-) positive, human epidermal growth factor receptor 2- (HER2-) negative early breast cancer. Methods. The records of nonmetastatic invasive breast cancer patients who underwent surgery at a single institution between 2009 and 2012 were reviewed. Primary end point was recurrence-free survival (RFS), and secondary end point was overall survival (OS). Ki-67 and PgR were assessed with immunohistochemistry for the tumor after surgery. Results. A total of 1848 patients were enrolled in this study. 223 (12%) patients had high (≥10%) Ki-67, and 1625 (88%) had low Ki-67 expression. Significantly worse RFS and OS were observed in the high vs. low Ki-67 expression only when the PgR was low (<20%) (p<0.001 and 0.005, respectively, for RFS and OS). There was no significant difference in RFS and OS according to Ki-67 when the PgR was high (p=0.120 and 0.076). RFS of four groups according to high/low Ki-67 and PgR expression was compared. The low PgR and high Ki-67 expression group showed worst outcome among them (p<0.001). In a multivariate analysis, high Ki-67 was an independent prognostic factor when the PgR was low (HR 3.05; 95% CI 1.50–6.19; p=0.002). Conclusions. Ki-67 had a value as a prognostic factor only under low PgR expression level in early breast cancer. PgR should be considered in evaluating the prognosis of breast cancer patients using Ki-67.

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Abstract P5-05-02: Prognostic impact of single-nucleotide polymorphisms (SNPs) in or near the ZNF423 and CTSO genes in estrogen receptor (ER)-positive breast cancer patients receiving adjuvant endocrine therapy

10.1158/1538-7445.sabcs14-p5-05-02 ◽

2015 ◽

Author(s):

Yukari Hato ◽

Yumi Endo ◽

Nobuyasu Yoshimoto ◽

Tomoko Asano ◽

Mina Yamaguchi ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Single Nucleotide Polymorphisms ◽

Cancer Patients ◽

Prognostic Impact ◽

Nucleotide Polymorphisms ◽

Breast Cancer Patients ◽

Single Nucleotide ◽

Er Positive ◽

Positive Breast Cancer

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Estrogen receptor beta as a prognostic factor in breast cancer patients: A systematic review and meta-analysis

Oncotarget ◽

10.18632/oncotarget.7219 ◽

2016 ◽

Vol 7 (9) ◽

pp. 10373-10385 ◽

Cited By ~ 25

Author(s):

Weige Tan ◽

Qian Li ◽

Kai Chen ◽

Fengxi Su ◽

Erwei Song ◽

...

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Estrogen Receptor ◽

Prognostic Factor ◽

Cancer Patients ◽

Meta Analysis ◽

Estrogen Receptor Beta ◽

Breast Cancer Patients ◽

Receptor Beta

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ESR1-Stabilizing Long Noncoding RNA TMPO-AS1 Promotes Hormone-Refractory Breast Cancer Progression

Molecular and Cellular Biology ◽

10.1128/mcb.00261-19 ◽

2019 ◽

Vol 39 (23) ◽

Cited By ~ 11

Author(s):

Yuichi Mitobe ◽

Kazuhiro Ikeda ◽

Takashi Suzuki ◽

Kiyoshi Takagi ◽

Hidetaka Kawabata ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Patients ◽

Endocrine Therapy ◽

Cancer Progression ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Breast Cancer Patients ◽

Er Positive ◽

Positive Breast Cancer

ABSTRACT Acquired endocrine therapy resistance is a significant clinical problem for breast cancer patients. In recent years, increasing attention has been paid to long noncoding RNA (lncRNA) as a critical modulator for cancer progression. Based on RNA-sequencing data of breast invasive carcinomas in The Cancer Genome Atlas database, we identified thymopoietin antisense transcript 1 (TMPO-AS1) as a functional lncRNA that significantly correlates with proliferative biomarkers. TMPO-AS1 positivity analyzed by in situ hybridization significantly correlates with poor prognosis of breast cancer patients. TMPO-AS1 expression was upregulated in endocrine therapy-resistant MCF-7 cells compared with levels in parental cells and was estrogen inducible. Gain and loss of TMPO-AS1 experiments showed that TMPO-AS1 promotes the proliferation and viability of estrogen receptor (ER)-positive breast cancer cells in vitro and in vivo. Global expression analysis using a microarray demonstrated that TMPO-AS1 is closely associated with the estrogen signaling pathway. TMPO-AS1 could positively regulate estrogen receptor 1 (ESR1) mRNA expression by stabilizing ESR1 mRNA through interaction with ESR1 mRNA. Enhanced expression of ESR1 mRNA by TMPO-AS1 could play a critical role in the proliferation of ER-positive breast cancer. Our findings provide a new insight into the understanding of molecular mechanisms underlying hormone-dependent breast cancer progression and endocrine resistance.

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