Open Access Research article

Nucleostemin expression in invasive breast cancer

Takayuki Kobayashi12, Kenkichi Masutomi3, Kenji Tamura4, Tomoyuki Moriya5, Tamio Yamasaki5, Yasuhiro Fujiwara4, Shunji Takahashi2, Junji Yamamoto5 and Hitoshi Tsuda16*

Author Affiliations

1 Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

2 Department of Medical Oncology, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan

3 Division of Cancer Stem Cell, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

4 Department of Breast Oncology and Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

5 Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

6 Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

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BMC Cancer 2014, 14:215  doi:10.1186/1471-2407-14-215

Published: 21 March 2014

Abstract

Background

Recently, the cancer stem cell hypothesis has become widely accepted. Cancer stem cells are thought to possess the ability to undergo self-renewal and differentiation, similar to normal stem cells. Nucleostemin (NS), initially cloned from rat neural stem cells, binds to various proteins, including p53, in the nucleus and is thought to be a key molecule for stemness. NS is expressed in various types of cancers; therefore, its role in cancer pathogenesis is thought to be important. This study was conducted to clarify the clinicopathological and prognostic impact of NS in invasive breast cancers.

Method

The correlation between NS immunoreactivity and clinicopathological parameters was examined in 220 consecutive surgically resected invasive breast cancer tissue samples by using tissue microarrays. The presence of nuclear NS and p53 immunoreactivity in 10% or more of cancer cells was considered as a positive result.

Results

Among the 220 patients, 154 were hormone-receptor (HR)-positive, 22 HER2-positive/HR-negative, and 44 HR-negative/HER2-negative. One hundred and forty-two tumors (64.5%) showed NS positivity, and this positivity was significantly correlated with estrogen receptor (ER) (P = 0.050), human epidermal growth factor receptor 2 (HER2) (P = 0.021), and p53 (P = 0.031) positivity. The patients with NS-positive tumors showed significantly shorter disease-free survival than those with NS-negative tumors. Furthermore, the patient group with NS- and p53-positive tumors showed significantly poorer prognosis than other patient groups. Multivariate analysis showed that NS status was an independent prognostic indicator.

Conclusions

NS may play a significant role in the determination of breast cancer progression in association with p53 alterations. The NS status of patients with luminal and HER2 type breast cancers may be a useful prognostic marker.