Subcellular localization of Mdm2 expression and prognosis of breast cancer

Hyung Seok Park; Ji Min Park; Seho Park; Junghoon Cho; Seung Il Kim; Byeong Woo Park

doi:10.1007/s10147-013-0639-1

Subcellular localization of Mdm2 expression and prognosis of breast cancer

Hyung Seok Park, Ji Min Park, Seho Park, Junghoon Cho, Seung Il Kim, Byeong Woo Park

Department of Surgery

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

Methods: p53 and Mdm2 expressions were determined by immunohistochemistry of tissue microarrays of 865 breast cancer patients who underwent surgery. Clinicopathological characteristics and survival data were analyzed. Mdm2 expression was categorized into four groups: negative, cytoplasm positive, nucleus positive, and concurrent nuclear and cytoplasm positive (N+&C+).

Background: Mouse double minute 2 (Mdm2) is a negative regulator of the tumor suppressor p53. The p53–Mdm2 pathway may play a role in cancer development and prognosis, although the role of p53–Mdm2 in breast cancer remains unclear.

Results: Negative, cytoplasm-positive, nucleus-positive, and N+&C+ expressions of Mdm2 were observed in 59.2, 10.9, 27.8, and 2.1 % of patients, respectively. The N+&C+ group was associated with larger tumor size, higher grade, negativity for estrogen and progesterone receptors, HER2 positivity, high Ki-67 index, p53 positivity, and triple negative breast cancer. p53-positive tumors showed poorer overall survival than p53-negative tumors. The nucleus-positive and N+&C+ groups showed poorer disease-free survival than the negative and cytoplasm-positive groups. In multivariate analysis, nuclear Mdm2 expression including the N+&C+ group was significantly related to poor prognosis.

Conclusions: Concurrent nuclear and cytoplasmic Mdm2 expression was an independent prognostic factor in patients with breast cancer. Subcellular localization of Mdm2 expression should be considered in the evaluation of Mdm2 in breast cancer.

Original language	English
Pages (from-to)	842-851
Number of pages	10
Journal	International Journal of Clinical Oncology
Volume	19
Issue number	5
DOIs	https://doi.org/10.1007/s10147-013-0639-1
Publication status	Published - 2014 Oct 16

Bibliographical note

Funding Information:
A major part of this study was presented at the 35th Annual San Antonio Breast Cancer Symposium poster session, 4–8 December 2012 in San Antonio, TX. This research has been supported by the Korea Breast Cancer Foundation, and was supported by the Brain Korea 21 Project for Medical Science at Yonsei University.

Publisher Copyright:
© 2013, Japan Society of Clinical Oncology.

All Science Journal Classification (ASJC) codes

Surgery
Hematology
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10147-013-0639-1

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title = "Subcellular localization of Mdm2 expression and prognosis of breast cancer",

abstract = "Methods: p53 and Mdm2 expressions were determined by immunohistochemistry of tissue microarrays of 865 breast cancer patients who underwent surgery. Clinicopathological characteristics and survival data were analyzed. Mdm2 expression was categorized into four groups: negative, cytoplasm positive, nucleus positive, and concurrent nuclear and cytoplasm positive (N+&C+).Background: Mouse double minute 2 (Mdm2) is a negative regulator of the tumor suppressor p53. The p53–Mdm2 pathway may play a role in cancer development and prognosis, although the role of p53–Mdm2 in breast cancer remains unclear.Results: Negative, cytoplasm-positive, nucleus-positive, and N+&C+ expressions of Mdm2 were observed in 59.2, 10.9, 27.8, and 2.1 % of patients, respectively. The N+&C+ group was associated with larger tumor size, higher grade, negativity for estrogen and progesterone receptors, HER2 positivity, high Ki-67 index, p53 positivity, and triple negative breast cancer. p53-positive tumors showed poorer overall survival than p53-negative tumors. The nucleus-positive and N+&C+ groups showed poorer disease-free survival than the negative and cytoplasm-positive groups. In multivariate analysis, nuclear Mdm2 expression including the N+&C+ group was significantly related to poor prognosis.Conclusions: Concurrent nuclear and cytoplasmic Mdm2 expression was an independent prognostic factor in patients with breast cancer. Subcellular localization of Mdm2 expression should be considered in the evaluation of Mdm2 in breast cancer.",

author = "Park, {Hyung Seok} and Park, {Ji Min} and Seho Park and Junghoon Cho and Kim, {Seung Il} and Park, {Byeong Woo}",

note = "Funding Information: A major part of this study was presented at the 35th Annual San Antonio Breast Cancer Symposium poster session, 4–8 December 2012 in San Antonio, TX. This research has been supported by the Korea Breast Cancer Foundation, and was supported by the Brain Korea 21 Project for Medical Science at Yonsei University. Publisher Copyright: {\textcopyright} 2013, Japan Society of Clinical Oncology.",

year = "2014",

month = oct,

day = "16",

doi = "10.1007/s10147-013-0639-1",

language = "English",

volume = "19",

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journal = "International Journal of Clinical Oncology",

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T1 - Subcellular localization of Mdm2 expression and prognosis of breast cancer

AU - Park, Hyung Seok

AU - Park, Ji Min

AU - Park, Seho

AU - Cho, Junghoon

AU - Kim, Seung Il

AU - Park, Byeong Woo

N1 - Funding Information: A major part of this study was presented at the 35th Annual San Antonio Breast Cancer Symposium poster session, 4–8 December 2012 in San Antonio, TX. This research has been supported by the Korea Breast Cancer Foundation, and was supported by the Brain Korea 21 Project for Medical Science at Yonsei University. Publisher Copyright: © 2013, Japan Society of Clinical Oncology.

PY - 2014/10/16

Y1 - 2014/10/16

N2 - Methods: p53 and Mdm2 expressions were determined by immunohistochemistry of tissue microarrays of 865 breast cancer patients who underwent surgery. Clinicopathological characteristics and survival data were analyzed. Mdm2 expression was categorized into four groups: negative, cytoplasm positive, nucleus positive, and concurrent nuclear and cytoplasm positive (N+&C+).Background: Mouse double minute 2 (Mdm2) is a negative regulator of the tumor suppressor p53. The p53–Mdm2 pathway may play a role in cancer development and prognosis, although the role of p53–Mdm2 in breast cancer remains unclear.Results: Negative, cytoplasm-positive, nucleus-positive, and N+&C+ expressions of Mdm2 were observed in 59.2, 10.9, 27.8, and 2.1 % of patients, respectively. The N+&C+ group was associated with larger tumor size, higher grade, negativity for estrogen and progesterone receptors, HER2 positivity, high Ki-67 index, p53 positivity, and triple negative breast cancer. p53-positive tumors showed poorer overall survival than p53-negative tumors. The nucleus-positive and N+&C+ groups showed poorer disease-free survival than the negative and cytoplasm-positive groups. In multivariate analysis, nuclear Mdm2 expression including the N+&C+ group was significantly related to poor prognosis.Conclusions: Concurrent nuclear and cytoplasmic Mdm2 expression was an independent prognostic factor in patients with breast cancer. Subcellular localization of Mdm2 expression should be considered in the evaluation of Mdm2 in breast cancer.

AB - Methods: p53 and Mdm2 expressions were determined by immunohistochemistry of tissue microarrays of 865 breast cancer patients who underwent surgery. Clinicopathological characteristics and survival data were analyzed. Mdm2 expression was categorized into four groups: negative, cytoplasm positive, nucleus positive, and concurrent nuclear and cytoplasm positive (N+&C+).Background: Mouse double minute 2 (Mdm2) is a negative regulator of the tumor suppressor p53. The p53–Mdm2 pathway may play a role in cancer development and prognosis, although the role of p53–Mdm2 in breast cancer remains unclear.Results: Negative, cytoplasm-positive, nucleus-positive, and N+&C+ expressions of Mdm2 were observed in 59.2, 10.9, 27.8, and 2.1 % of patients, respectively. The N+&C+ group was associated with larger tumor size, higher grade, negativity for estrogen and progesterone receptors, HER2 positivity, high Ki-67 index, p53 positivity, and triple negative breast cancer. p53-positive tumors showed poorer overall survival than p53-negative tumors. The nucleus-positive and N+&C+ groups showed poorer disease-free survival than the negative and cytoplasm-positive groups. In multivariate analysis, nuclear Mdm2 expression including the N+&C+ group was significantly related to poor prognosis.Conclusions: Concurrent nuclear and cytoplasmic Mdm2 expression was an independent prognostic factor in patients with breast cancer. Subcellular localization of Mdm2 expression should be considered in the evaluation of Mdm2 in breast cancer.

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JO - International Journal of Clinical Oncology

JF - International Journal of Clinical Oncology

SN - 1341-9625

IS - 5

ER -

Subcellular localization of Mdm2 expression and prognosis of breast cancer

Abstract

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