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Jagged1 modulated tumor-associated macrophage differentiation predicts poor prognosis in patients with invasive micropapillary carcinoma of the breast.

Abstract Invasive micropapillary carcinoma of the breast (IMPC) constitutes a unique and aggressive subtype of breast cancer. We aimed to evaluate the prognostic significance of the Jagged1 (a ligand of the Notch pathway) expression, and infiltration density of tumor-associated macrophages (TAMs) in patients with IMPC.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title medicine
Publication Year Start




PMID- 28422875
OWN - NLM
STAT- In-Process
DA  - 20170419
LR  - 20170419
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Linking)
VI  - 96
IP  - 16
DP  - 2017 Apr
TI  - Jagged1 modulated tumor-associated macrophage differentiation predicts poor
      prognosis in patients with invasive micropapillary carcinoma of the breast.
PG  - e6663
LID - 10.1097/MD.0000000000006663 [doi]
AB  - OBJECTIVES: Invasive micropapillary carcinoma of the breast (IMPC) constitutes a 
      unique and aggressive subtype of breast cancer. We aimed to evaluate the
      prognostic significance of the Jagged1 (a ligand of the Notch pathway)
      expression, and infiltration density of tumor-associated macrophages (TAMs) in
      patients with IMPC. METHODS: Jagged1 expression and CD163+, CD68+ macrophage
      infiltration were evaluated by immunohistochemistry in 222 tumor samples, and the
      clinical significance was analyzed. mRNA level of Jagged1 was analyzed by real
      time PCR in tumor tissues. RESULTS: The IMPC patients showed larger tumor size,
      more lymphatic invasion, higher expression levels of estrogen receptor (ER),
      increased Ki67 index, higher Jagged1 protein level, and denser infiltration of
      CD163+ macrophages compared to patients with invasive breast ductal carcinoma. In
      the IMPC cohort, positive Jagged1 expression was related to aggressive features
      including large tumor size, lymphatic invasion, and Ki67 overexpression.
      Statistical significance was found between CD163+ macrophage infiltration and
      Jagged1 expression levels. Cox regression analysis revealed that ER negativity,
      positive Jagged1 expression, and a high degree of CD163+ macrophage infiltration 
      were independent prognostic factors for disease-free survival, and positive
      Jagged1 expression was an independent prognostic factor for overall survival. The
      level of Jagged1 mRNA was higher in tumor tissues of patients with IMPC.
      CONCLUSION: Jagged1, by modulating TAMs infiltration, is associated with a less
      favorable prognosis for patients with IMPC. Our results have important
      implications for therapies targeting Jagged1-Notch signaling and re-educating
      TAMs polarization for patients with IMPC.
FAU - Liu, Hang
AU  - Liu H
AD  - aDepartment of Medical Oncology, Tumor Hospital of Harbin Medical University
      bCancer Research Institute of Harbin Medical University cDepartment of Medical
      Oncology, Harbin Chest Hospital, Harbin, Heilongjiang Province, China.
FAU - Wang, Jingxuan
AU  - Wang J
FAU - Liu, Zhaoliang
AU  - Liu Z
FAU - Wang, Le
AU  - Wang L
FAU - Liu, Shoujun
AU  - Liu S
FAU - Zhang, Qingyuan
AU  - Zhang Q
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
EDAT- 2017/04/20 06:00
MHDA- 2017/04/20 06:00
CRDT- 2017/04/20 06:00
AID - 10.1097/MD.0000000000006663 [doi]
AID - 00005792-201704210-00056 [pii]
PST - ppublish
SO  - Medicine (Baltimore). 2017 Apr;96(16):e6663. doi: 10.1097/MD.0000000000006663.

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