title: The chemokine receptor CXCR4 is more frequently expressed in breast compared to other metastatic adenocarcinomas in effusions.
abstract: This objective of this study was to investigate the expression of chemokine receptors in tumor cells and leukocytes in breast carcinoma effusions. The expression of leukocyte markers (CD3/4/8/14/16/19) and chemokine receptors (CXCR1/4, CCR2/5/7) was studied in 21 breast carcinoma effusions using flow cytometry. Breast carcinoma cells expressed CXCR4 in 7/21 (33%) effusions, with less frequent expression of CXCR1, CCR5, and CCR7. CXCR2 and CCR2 were absent. Lymphocytes showed frequent CXCR4, CCR5, and CCR7 expression, while CXCR1, CXCR2, CCR2 were rarely or never detected. Macrophages expressed all six receptors except for CXCR2. Comparative analysis of breast carcinoma effusions with previously studied ovarian and cervical/endometrial adenocarcinomas (ACs) showed significantly higher CXCR4 expression in breast carcinoma cells compared to the other gynecological ACs (p = 0.001). Breast and cervical/endometrial carcinoma effusions showed different expression of chemokine receptors in lymphocytes (lower CXCR1, higher CXCR4 and CCR7 levels; p = 0.012, p = 0.005, p < 0.001, respectively) and macrophages (higher CCR7 levels; p < 0.001), as well as lower CD8 counts (p < 0.001) and higher CD19 counts (p = 0.001) compared to ovarian carcinoma effusions. Higher numbers of CD8-positive lymphocytes (p = 0.080) and higher CCR7 monocyte expression (p = 0.087) were associated with a trend for shorter disease-free survival. In conclusion, breast carcinoma cells express CXCR4, a unique feature among metastatic ACs in effusions, with rare expression of other chemokine receptors. Chemokine receptor expression in leukocytes and lymphocyte counts significantly differ from those of ovarian carcinoma effusions. The prognostic role of CCR7 expression in monocytes and CD8 counts in breast carcinoma effusions merits further research.
authors.affiliation: Pathology Clinic, Rikshospitalet Medical Center, Montebello, Oslo, Norway. ben.davidson@radiumhospitalet.no
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.forename: Hiep Phuc
authors.initials: HP
authors.lastname: Dong
authors.forename: Arild
authors.initials: A
authors.lastname: Holth
authors.forename: Aasmund
authors.initials: A
authors.lastname: Berner
authors.forename: Björn
authors.initials: B
authors.lastname: Risberg
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D015331:Cohort Studies; D005122:Exudates and Transudates / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000032:analysis / Q000378:metabolism*; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019718:Receptors, CXCR4