Elsevier

Human Pathology

Volume 41, Issue 8, August 2010, Pages 1186-1195
Human Pathology

Original contribution
Prognostic value of the X-linked inhibitor of apoptosis protein for invasive ductal breast cancer with triple-negative phenotype

https://doi.org/10.1016/j.humpath.2010.01.013Get rights and content

Summary

Molecular classification has raised new hopes of improving our understanding of breast cancer. Discovery of novel tumor markers that allow the identification of patients at higher risk for invasive ductal breast cancer with triple-negative phenotype remains a research and clinical priority. To evaluate the prognostic value of the X-linked inhibitor of apoptosis protein for invasive ductal breast cancer with triple-negative phenotype by correlating the expression of X-linked inhibitor of apoptosis protein with clinicopathologic parameters, thus determining its role in predicting tumor outcomes, 200 cases of patients with invasive ductal breast cancer, including their complete information, were obtained. Tissue microarrays were constructed; and immunohistochemical staining was performed to detect the expression of the estrogen receptor, progesterone receptor, HER2/neu, Ki-67, and X-linked inhibitor of apoptosis protein. We identified 42 cases of invasive ductal breast cancer with triple-negative phenotype. Of these, X-linked inhibitor of apoptosis protein expression was detected in 32 patients (80%). Significant correlations were found between X-linked inhibitor of apoptosis protein expression and primary tumor size (P = .027), and between X-linked inhibitor of apoptosis protein expression and Ki-67 index (P = .038). Kaplan-Meier survival analysis revealed a pattern of X-linked inhibitor of apoptosis protein expression with impaired overall and disease-free survival in patients with the disease. Most importantly, multivariate analysis also showed statistically significant worse outcomes for patients with tumors exhibiting X-linked inhibitor of apoptosis protein expression of at least 50% compared with those with X-linked inhibitor of apoptosis protein expression less than 50%. In conclusion, our results suggest that X-linked inhibitor of apoptosis protein is a novel biomarker and viable prognostic factor for invasive ductal breast cancer with triple-negative phenotype. Furthermore, the expression of X-linked inhibitor of apoptosis protein is significantly correlated with a more aggressive tumor phenotype and decreased overall and disease-free survival.

Introduction

Breast cancer remains a main leading cause of morbidity and mortality in women all over the world, especially in developing countries including China [1]. During the past several years, great progress has been achieved based on the gene expressions profile generated by DNA microarray analysis. As such, breast cancer can now be redefined into 5 molecular subtypes, each of which is associated with distinct clinical implications [2], [3]. Triple-negative breast cancers (TNBCs) are characterized by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and HER2/neu [4]. TNBCs account for 15% to 24% of all invasive ductal breast cancers of no specific type, are characterized by very aggressive biological behavior, and are associated with poor clinical prognoses compared with other types of cancer [5], [6]. Furthermore, it should be emphasized that TNBCs are composed of a heterogeneous group of tumors [6], [7]. Thus, the identification of tumor markers that allow the identification of patients at higher risk for invasive ductal breast cancer with triple-negative phenotype remains a research and clinical priority. At present, however, research on detecting factors that affect prognosis of invasive ductal TNBC has not been performed thoroughly.

Inhibitors of apoptotic proteins are a more recently described family of proteins that includes the X-linked inhibitor of apoptosis protein (XIAP), which acts by directly inhibiting caspases. There are little data about XIAP roles in invasive ductal breast cancer with triple-negative phenotype. Thus, the aim of this study is to evaluate the possible prognostic role of XIAP in invasive ductal breast cancer with triple-negative phenotype.

Section snippets

Patients and tissues

Two hundred patients diagnosed with invasive ductal breast cancer between January 1997 and January 2004 at the Department of Pathology of Tianjin Medical University General Hospital were enrolled in this study. The study was approved by the ethics committees of Tianjin Medical University, and written informed consent was obtained from all participating patients. All patients had complete clinicopathologic information, including age, menopause status, tumor size, and number of axillary-positive

Patient and primary tumor characteristics

Patient and primary tumor characteristics are presented in Table 1. Among 200 patients diagnosed with invasive ductal breast cancer, 42 lacked ER, PR, and HER2 expression. All 42 patients were women with a mean age of 48.83 ± 9.59 years (range, 32-69 years); 23 (54.76%) patients were between the ages of 35 and 49 years, and 16 (38.10%) patients were aged more than 50 years. At the time of breast cancer surgery, 15 (35.71%) patients were postmenopausal and 27 (64.29%) were premenopausal.

Discussion

Breast cancer, the most common malignant solid tumor occurring in women, consists of a wide variety of histologic types with different clinical behaviors and outcomes. Current breast cancer histopathologic classification systems are based on several descriptive entities that are of prognostic significance. For a long time, traditional clinicopathologic factors such as lymph node status, tumor size, microvessel density, and histologic grade were considered to be the most useful prognostic

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      Among them, the third one, BIR3, has been widely recognized since more than a decade as a valuable anticancer target (Holcik et al., 2001; Zobel et al., 2006). Recently, as a cancer biomarker, the prognostic value of XIAP in the early-stages cancer has attracted much attention (Moussata et al., 2012; Wang et al., 2010; Yang et al., 2008). A high specific and sensitive detection method of XIAP would be interesting for clinical diagnosis of early-stages cancer and cancer cell resistance during radio- or chemo-therapy (Sun et al., 2004, 2009; Zobel et al., 2006).

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    Supported by the Tianjin Natural Science Foundation (06YFJMJC08000 and 09ZCZDSF04400) from Tianjin, PR China, and a science grant from Tianjin Medical University (2008KY06), Tianjin, PR China.

    1

    These authors contributed equally to this work.

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