eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
Current issue Archive Manuscripts accepted About the journal Supplements Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
4/2018
vol. 69
 
Share:
Share:
more
 
 
abstract:
Original paper

Distribution of CXCR4 and tumour-infiltrating lymphocytes in breast cancer subtypes; their relationship with each other, axillary lymph node involvement, and other prognostic indicators

Fatma S. Pehlivan, Oya N. Sivrikoz, Filiz Dag, Sibel D. Kececi, Salahattin M. Sanal

Pol J Pathol 2018; 69 (4): 335-341
Online publish date: 2019/01/31
View full text
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
We have investigated the distribution of chemokine receptor 4 (CXCR4) and CD8-positive, tumour-infiltrating T lymphocytes (CD8+ TILs) in breast cancer subtypes and explored the relationship between them and the well-established conventional prognostic markers, including axillary lymph node involvement.

A total of 250 breast cancer patients were included in the study. The patients were separated into luminal A+B, HER2 enriched/overexpressed (HER2+), and triple-

negative, on the basis of their staining characteristics, via conventional staining methods. Immunohistochemical (IHC) staining for CXCR4 and CD8+ TILs were performed on the archival tissues from each patient.

With increasing intensity of CXCR4 staining, there was a higher incidence of lymph node metastasis (p < 0.01). Similarly, there was a positive correlation between the primary tumour size, HER2+ subtype, lymphovascular invasion, and axillary lymph node involvement. Dense lymphocytic infiltration was observed in HER2+ and triple-negative patients. No correlation between CD8+ TILs in all sites and breast cancer subtypes was discovered. A reverse correlation was discovered with CD8+ TILs stained only intratumorally and CXCR4 expression.

In conclusion, lymph node involvement correlates with higher CXCR4 expression in all breast cancer subtypes. Conversely, no such correlation is found with CD8+ TILs.
keywords:

breast cancer, breast cancer subtype, CXCR4, tumour-infiltrating lymphocytes

references:
Mahmoud MA, Paish EM, Powe DG, et al. Tumor-Infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 2011; 29: 1949-1955.
Denkert C, Loibl S, Noske A, et al. Tumor associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin. Oncol 2010; 28: 105-113.
Denkert C, Minckwitz G, Brase JC, et al. Tumor-Infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2 – positive and triple negative primary breast cancer.
J Clin Oncol 2015; 33: 983-991.
Loi S, Sirtaine N, Piette F, et al. Prognostic and predictive value of tumor-Infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin- based chemotherapy: BIG 02-98. J Clin Oncol 2013; 31: 860-870.
Adams S, Gray RJ, Demaria S, et al. Prognostic value of tumor-Infiltrating lymphocytes in triple negative breast cancer from two phase III randomized adjuvant breast cancer trial: ECOG 2197 and ECOG 1199. J Clin Oncol 2014; 32: 2959-2967.
Ali HR, Glont SE, Blows FM, et al. PD-L1 protein Expression in Breast Cancer is rare, Enriched in Basal-like Tumours and Associated with Infiltrating lymphocytes. Ann Oncol 2015; 26: 1488-1493.
Muller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001; 410: 50-56.
Hwang JH, Hwang JH, Chung HK, et al. CXC chemokine receptor 4 expression and function in human anaplastic thyroid cancer cells. J Clin Endocrinol Metab 2003; 88: 408-416.
Schrader AJ, Lechner O, Templin M, et al. CXCR4/CXCL12 expression and signaling in kidney cancer. Br J Cancer 2002; 86: 1250-1256.
Voduc KD, Cheang MCU, Tyldesly S, et al. Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 2010: 28: 1684-1691.
Salgado R, Denkert C, Demaria S, et al. The Evaluation of Tumor-Infiltrating Lymphocytes (TILs) in Breast Cancer: Recommendations by an International TILs Working Group 2014. Ann Oncol 2015; 26: 259-271.
Bukholm IK, Nesland JM, Borresen D, et al. Re-expression of E-cadherin, alpha-catenin and beta-catenin, but not of gamma-
catenin, in metastatic tissue from breast cancer patients.
J Pathol 2000; 190: 15-19.
Yasuoka H, Tsujimoto M, Yoshidome K, et al. Cytoplasmic CXCR4 expression in breast cancer: induction by nitric oxide and correlation with lymph node metastasis and poor prognosis. BMC Cancer 2008; 8: 340.
Adamkov M, Halasova E, Kajo K, et al. Survivin: a promising biomarker in breast carcinoma. Neoplasma 2010; 57: 572-577.
Zhao Z, Lu P, Zhang H, et al. Nestin positively regulates the Wnt/β-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells. Breast Cancer Res 2014; 16: 408-420.
Liotta LA, Kohn EC. The microenvironment of the tumour-host-interface. Nature 2001; 411: 375-379.
Vela M, Aris M, Llorente M, et al. Chemokine receptor-specific antibodies in cancer immunotherapy: achievements and challenges. Front Immunol 2015; 6: 12.
Cabioglu N, Yazici MS, Arun B, et al. CCR7 and CXCR4 as novel biomarkers predicting axillary lymph node metastasis in T1 breast cancer. Clin Cancer Res 2005; 11: 5686-5693.
Chu QD, Holm NT, Madumere P, et al. Chemokine receptor CXCR4 overexpression predicts recurrence for hormone receptor-positive, node-negative breast cancer patients. Surgery 2011; 149: 193-199.
Sivrikoz ON, Doğanay L, Sivrikoz UK, et al. Distribution CXCR4 and gamma-catenin expression pattern in breast cancer subtypes and their relationship to axillary nodal involvement. Pol J Pathol 2013; 64: 253-259.
Zhang Z, Ni C, Chen W, et al. Expression of CXCR4 and breast cancer prognosis: a systematic review and meta-analysis. BMC Cancer 2014; 14: 49.
Liu Y, Li J, Gu X, et al. Correlation effect of EGFR and CXCR4 and CCR7 chemokine receptors in predicting breast cancer metastasis and prognosis. J Exp Clin Cancer Res 2010; 29: 16-25.
Mueller A, Homey B, Soto H, et al. Involvement of the chemokine receptors in breast cancer metastasis. Nature 2001; 410: 50-56.
Ali HR, Provenzano E, Dawson SJ, et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12439 patients. Ann Oncol 2014; 25: 1536-1543.
Ibrahim EM, Al-Foheidi ME, Al-Mansour MM, et al.
The prognostic value of tumor-infiltrating lymphocytes in triple-
negative breast cancer: a meta-analysis Breast Cancer Res Treat 2014; 148: 467-476.
Macchetti AH, Marana HRC, Silva JS, et al. Tumor-infiltrating CD4+ T lymphocytes in early breast cancer reflect lymph node involvement. Clinics 2006; 61: 203-208.
Matkowski R, Gisterek I, Halon A. The Prognostic Role of Tumor-infiltrating CD4 and CD8 T Lymphocytes in Breast Cancer. Anticancer Res 2009; 29: 2445-2452.
Khedr RAG, Ghannam AA, Rashidy MA, et al. The prognostic role of tumor-infiltrating lymphocytes CD8 and Foxp3 and their impact on recurrence in breast cancer patients. J Cancer Sci Ther 2016; 8: 7.
Zhang S, Zhang D, Gong M, et al. High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer. BMC Cancer 2017; 17: 335.
Howland K, Driver T, Sedrak M. Lymph node involvement in immunohistochemistry-based molecular classifications of breast cancer. J Surg Res 2013; 185: 697-703.
Seok Park H, Heo I, Ye Kim J, et al. No effect of tumor-infiltrating lymphocytes (TILs) on prognosis in patients with early triple-negative breast cancer: Validation of recommendations by the International TILs Working Group 2014. J Surg Oncol 2016; 114: 17-21.
FEATURED PRODUCTS
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe