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      High Cytoplasmic CXCR4 Expression Predicts Prolonged Survival in Triple-Negative Breast Cancer Patients Treated with Adjuvant Chemotherapy

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      https://www.riss.kr/link?id=A105942076

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      다국어 초록 (Multilingual Abstract)

      Background: Chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand CXC motif chemokine 12 (CXCL12; stromal cell-derived factor-1) are implicated in tumor growth, metastasis, and tumor cell-microenvironment interaction. A number of stu...

      Background: Chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand CXC motif chemokine 12 (CXCL12; stromal cell-derived factor-1) are implicated in tumor growth, metastasis, and tumor cell-microenvironment interaction. A number of studies have reported that increased CXCR4 expression is associated with worse prognosis in triple-negative breast cancer (TNBC), but its prognostic significance has not been studied in TNBC patients treated with adjuvant chemotherapy. Methods: Two hundred eighty-three TNBC patients who received adjuvant chemotherapy were retrospectively analyzed. Tissue microarray was constructed from formalinfixed, paraffin-embedded tumor tissue and immunohistochemistry for CXCR4 and CXCL12 was performed. Expression of each marker was compared with clinicopathologic characteristics and outcome. Results: High cytoplasmic CXCR4 expression was associated with younger age (p = .008), higher histologic grade (p = .007) and lower pathologic stage (p = .045), while high CXCL12 expression was related to larger tumor size (p = .045), positive lymph node metastasis (p = .005), and higher pathologic stage (p = .017). The patients with high cytoplasmic CXCR4 experienced lower distant recurrence (p = .006) and better recurrence-free survival (RFS) (log-rank p = .020) after adjuvant chemotherapy. Cytoplasmic CXCR4 expression remained an independent factor of distant recurrence (p = .019) and RFS (p = .038) after multivariate analysis. Conclusions: High cytoplasmic CXCR4 expression was associated with lower distant recurrence and better RFS in TNBC patients treated with adjuvant chemotherapy. This is the first study to correlate high CXCR4 expression to better TNBC prognosis, and the underlying mechanism needs to be elucidated in further studies.

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      참고문헌 (Reference)

      1 Liu Y, "orrelation effect of EGFR and CXCR4 and CCR7 chemokine receptors in predicting breast cancer metastasis and prognosis" 29 : 16-, 2010

      2 Bianchini G, "Triplenegative breast cancer: challenges and opportunities of a heterogeneous disease" 13 : 674-690, 2016

      3 Boyle P, "Triple-negative breast cancer: epidemiological considerations and recommendations" 23 (23): vi7-vi12, 2012

      4 Salvucci O, "The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study" 97 : 275-283, 2006

      5 Hassan S, "The influence of tumor-host interactions in the stromal cell-derived factor-1/CXCR4 ligand/receptor axis in determining metastatic risk in breast cancer" 175 : 66-73, 2009

      6 Orimo A, "Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion" 121 : 335-348, 2005

      7 Kang H, "Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer" 7 : R402-R410, 2005

      8 Haribabu B, "Regulation of human chemokine receptors CXCR4. Role of phosphorylation in desensitization and internalization" 272 : 28726-28731, 1997

      9 Yan M, "Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers" 13 : R47-, 2011

      10 Wolff AC, "Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update" 31 : 3997-4013, 2013

      1 Liu Y, "orrelation effect of EGFR and CXCR4 and CCR7 chemokine receptors in predicting breast cancer metastasis and prognosis" 29 : 16-, 2010

      2 Bianchini G, "Triplenegative breast cancer: challenges and opportunities of a heterogeneous disease" 13 : 674-690, 2016

      3 Boyle P, "Triple-negative breast cancer: epidemiological considerations and recommendations" 23 (23): vi7-vi12, 2012

      4 Salvucci O, "The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study" 97 : 275-283, 2006

      5 Hassan S, "The influence of tumor-host interactions in the stromal cell-derived factor-1/CXCR4 ligand/receptor axis in determining metastatic risk in breast cancer" 175 : 66-73, 2009

      6 Orimo A, "Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion" 121 : 335-348, 2005

      7 Kang H, "Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer" 7 : R402-R410, 2005

      8 Haribabu B, "Regulation of human chemokine receptors CXCR4. Role of phosphorylation in desensitization and internalization" 272 : 28726-28731, 1997

      9 Yan M, "Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers" 13 : R47-, 2011

      10 Wolff AC, "Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update" 31 : 3997-4013, 2013

      11 Hudis CA, "Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system" 25 : 2127-2132, 2007

      12 Elston CW, "Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up" 19 : 403-410, 1991

      13 Muller A, "Involvement of chemokine receptors in breast cancer metastasis" 410 : 50-56, 2001

      14 Yu S, "High level of CXCR4 in triplenegative breast cancer specimens associated with a poor clinical outcome" 67 : 369-375, 2013

      15 Chu QD, "High chemokine receptor CXCR4 level in triple negative breast cancer specimens predicts poor clinical outcome" 159 : 689-695, 2010

      16 Zou YR, "Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development" 393 : 595-599, 1998

      17 Kobayashi T, "Expression pattern of stromal cell-derived factor-1 chemokine in invasive breast cancer is correlated with estrogen receptor status and patient prognosis" 123 : 733-745, 2010

      18 Zhang Z, "Expression of CXCR4 and breast cancer prognosis: a systematic review and meta-analysis" 14 : 49-, 2014

      19 Nagasawa T, "Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1" 382 : 635-638, 1996

      20 Chen HW, "Cytoplasmic CXCR4 high-expression exhibits distinct poor clinicopathological characteristics and predicts poor prognosis in triple-negative breast cancer" 13 : 410-416, 2013

      21 Baggiolini M, "Chemokines and leukocyte traffic" 392 : 565-568, 1998

      22 Balkwill F, "Cancer and the chemokine network" 4 : 540-550, 2004

      23 Smith MC, "CXCR4 regulates growth of both primary and metastatic breast cancer" 64 : 8604-8612, 2004

      24 Lefort S, "CXCR4 inhibitors could benefit to HER2 but not to triple-negative breast cancer patients" 36 : 1211-1222, 2017

      25 Mirisola V, "CXCL12/SDF1 expression by breast cancers is an independent prognostic marker of diseasefree and overall survival" 45 : 2579-2587, 2009

      26 Guo F, "CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks" 35 : 816-826, 2016

      27 Alda Losi Guembarovski, "CXCL12 chemokine and CXCR4 receptor: association with susceptibility and prognostic markers in triple negative breast cancer" Springer Nature 45 (45): 741-750, 2018

      28 Hammond ME, "American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer" 28 : 2784-2795, 2010

      29 Lebert JM, "Advances in the systemic treatment of triple-negative breast cancer" 25 (25): S142-S150, 2018

      30 Domanska UM, "A review on CXCR4/CXCL12 axis in oncology: no place to hide" 49 : 219-230, 2013

      31 Samarendra H, "A meta-analysis of CXCL12 expression for cancer prognosis" 117 : 124-135, 2017

      32 Huang EH, "A CXCR4 antagonist CTCE-9908 inhibits primary tumor growth and metastasis of breast cancer" 155 : 231-236, 2009

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      학술지 이력

      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
      2020-01-01 평가 등재학술지 유지 (해외등재 학술지 평가) KCI등재
      2014-12-24 학술지명변경 한글명 : The Korean Journal of Pathology -> Journal of Pathology and Translational Medicine
      외국어명 : The Korean Journal of Pathology -> Journal of Pathology and Translational Medicine
      KCI등재
      2010-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-04-13 학술지명변경 한글명 : 대한병리학회지 -> The Korean Journal of Pathology KCI등재
      2007-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2005-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2002-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      1999-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.13 0.13 0.12
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.13 0.11 0.409 0.01
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