Expression of CXCR4 and SDF-1αin Primary Breast Cancers and Metastatic Lymph Nodes

다국어 초록 (Multilingual Abstract)

Purpose: A CXCR4/stroma derived factor-1α(SDF-1α, CXCL12) interaction is involved in many metastatic cancer mechanisms, including breast cancer. The primary objectives of this study were to investigate the correlation between CXCR4 and axillary lymph node metastasis and to clarify the interaction between CXCR4 in primary tumor cells and SDF-1αin metastatic lymph nodes. An analysis of the correlation between CXCR4, SDF-1αand clinicopathologic features was also performed. Methods: Representative
areas from 44 invasive ductal carcinomas were selected for construction of tissue microarrays using a 5 mm punch. Breast cancers (n=44), metastatic axillary lymph nodes (n=18) and non-metastatic axillary lymph nodes (n=26) were immunohistochemically stained for CXCR4, SDF-1α, estrogen receptor
(ER), progesterone receptor (PR) and HER2. The parameters of age, tumor size, nuclear grade, histologic grade, lymph node status and pathologic node (pN) stage pN0 to pN3 were evaluated. Results: CXCR4 expression was negatively correlated with increased age (p=0.005) and positively correlated with a large tumor size (p=0.043) and PR expression (p=0.027). CXCR4 expression was not correlated with metastatic lymph nodes (p=0.079) and SDF-1αexpression in metastatic lymph nodes (p=0.062). However, CXCR4
nuclear positivity is correlated with lymph node metastasis (p=0.044). SDF-1αwas not correlated with any clinicopathologic feature in a statistically significant manner. Conclusion: An evaluation of young age, large tumor size and PR expression helps predict lymph node metastasis and poor prognosis.
Expression of CXCR4 nuclear positivity is correlated with a poor prognosis.

참고문헌 (Reference)

1 Balkwill F, "The significance of cancer cell expression of the chemokine receptor CXCR4" 14 : 171-179, 2004

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

3 Kang H, "The elevated level of CXCR4 is correlated with nodal metastasis of human breast cancer" 14 : 360-367, 2005

4 Wagner PL, "The chemokine receptors CXCR4 and CCR7 are associated with tumor size and pathologic indicators of tumor aggressiveness in papillary thyroid" 15 : 2833-2841, 2008

5 Pan J, "Stromal derived factor-1 (SDF-1/CXCL12) and CXCR4 in renal cell carcinoma metastasis" 5 : 56-, 2006

6 Dewan MZ, "Stromal cell-derived factor-1 and CXCR4 receptor interaction in tumor growth and metastasis of breast cancer" 60 : 273-276, 2006

7 Tsoli E, "Simultaneous evaluation of maspin and CXCR4 in patients with breast cancer" 60 : 261-266, 2007

8 Woo SU, "Significant correlation between nuclear CXCR4 expression and axillary lymph node metastasis in hormonal receptor negative breast cancer" 15 : 281-285, 2008

9 Kijima T, "Regulation of cellular proliferation, cytoskeletal function, and signal transduction through CXCR4 and c-Kit in small cell lung cancer cells" 62 : 6304-6311, 2002

10 Fernandis AZ, "Regulation of CXCR4 mediated chemotaxis and chemoinvasion of breast cancer cells" 23 : 157-167, 2004

11 Uchida D, "Possible role of stromal-cell-derived factor-1/CXCR4 signaling on lymph node metastasis of oral squamous cell carcinoma" 290 : 289-302, 2003

12 Nicolson GL, "Paracrine and autocrine growth mechanisms in tumor metastasis to specific sites with particular emphasis on brain and lung metastasis" 12 : 325-343, 1993

13 Helbig G, "NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4" 278 : 21631-21638, 2003

14 Shim HS, "Lower expression of CXCR4 in lymph node metastases than in primary breast cancers: Potential regulation by ligand-dependent degradation and HIF-1a" 346 : 252-258, 2006

15 Liu F, "Increased expression of SDF-1/CXCR4 is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast" 54 : 741-750, 2009

16 Adams GB, "Heterologous cells cooperate to augment stem cell migration, homing, and engraftment" 101 : 45-51, 2003

17 Möhle R, "Functional response of leukaemic blasts to stromal cell-derived factor-1 correlates with preferential expression of the chemokine receptor CXCR4 in acute myelomonocytic and lymphoblastic leukaemia" 110 : 563-572, 2000

18 Su YC, "Expression of CXCR4 is associated with axillary lymph node status in patients with early breast cancer" 15 : 533-539, 2006

19 Sun YX, "Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo" 89 : 462-473, 2003

20 Harvey JM, "Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer" 17 : 1474-1481, 1999

21 Bae YK, "Estrogen receptor expression in Korean breast carcinoma and comparison of three anti-ER antibodies. abstract #4" 43-, 2009

22 Scotton CJ, "Epithelial cancer cell migration: a role for chemokine receptors?" 61 : 4961-4965, 2001

23 Cabioglu N, "Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow" 22 : 39-46, 2005

24 Spano JP, "Chemokine receptor CXCR4 and early stage non-small cell lung cancer: pattern of expression and correlation with outcome" 15 : 613-617, 2004

25 Cabioglu N, "CCR7 and CXCR4 as novel biomarkers predicting axillary lymph node metastasis in T1 breast cancer" 11 : 5686-5693, 2005

26 송준선, "Association of CXCR4 Expression with Metastasis and Survival among Patients with Non-small Cell Lung Cancer" 대한병리학회 42 (42): 358-364, 2008

27 Geminder H, "A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived factor-1, in the development of bone marrow metastases in neuroblastoma" 167 : 4747-4757, 2001