title: Brain metastasis in renal cancer patients: metastatic pattern, tumour-associated macrophages and chemokine/chemoreceptor expression.
abstract: BACKGROUND
  The mechanisms of brain metastasis in renal cell cancer (RCC) patients are poorly understood. Chemokine and chemokine receptor expression may contribute to the predilection of RCC for brain metastasis by recruitment of monocytes/macrophages and by control or induction of vascular permeability of the blood-brain barrier.
  
  
  METHODS
  Frequency and patterns of brain metastasis were determined in 246 patients with metastatic RCC at autopsy. Expression of CXCR4, CCL7 (MCP-3), CCR2 and CD68(+) tumour-associated macrophages (TAMs) were analysed in a separate series of 333 primary RCC and in 48 brain metastases using immunohistochemistry.
  
  
  RESULTS
  Fifteen percent of 246 patients with metastasising RCC had brain metastasis. High CXCR4 expression levels were found in primary RCC and brain metastases (85.7% and 91.7%, respectively). CCR2 (52.1%) and CCL7 expression (75%) in cancer cells of brain metastases was more frequent compared with primary tumours (15.5% and 16.7%, respectively; P<0.0001 each). The density of CD68(+) TAMs was similar in primary RCC and brain metastases. However, TAMs were more frequently CCR2-positive in brain metastases than in primary RCC (P<0.001).
  
  
  CONCLUSIONS
  Our data demonstrate that the monocyte-specific chemokine CCL7 and its receptor CCR2 are expressed in tumour cells of RCC. We conclude that monocyte recruitment by CCR2 contributes to brain metastasis of RCC.
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: L
authors: L
authors: Wyler
authors: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors: C U
authors: CU
authors: Napoli
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: B
authors: B
authors: Ingold
authors: Clinic for Urology, University Hospital Zurich, Zurich, Switzerland.
authors: T
authors: T
authors: Sulser
authors: Institute of Virology, Technische Universität München (TUM), Helmholtz Zentrum München (HMGU), München, Germany.
authors: M
authors: M
authors: Heikenwälder
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: P
authors: P
authors: Schraml
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: H
authors: H
authors: Moch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001344:Autopsy; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D054410:Chemokine CCL7 / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D054390:Receptors, CCR2 / Q000096:biosynthesis*; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D054410:Chemokine CCL7; D054390:Receptors, CCR2; D019718:Receptors, CXCR4; C515450:CCL7 protein, human; C515334:CCR2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C527276:CXCR4 protein, human