title: Reduced expression of CXCR4, a novel renal cancer stem cell marker, is associated with high-grade renal cell carcinoma.
abstract: OBJECTIVE
  Cancer stem cells (CSCs) represent a population with tumour-initiating, self-renewal, and differentiation potential. This study aimed to evaluate the expression patterns and clinical significance of chemokine receptor type 4 (CXCR4) as a novel CSC marker in renal cell carcinoma (RCC).
  
  
  METHODS
  The expression of CXCR4 was examined in 173 well-defined renal tumour tissues, including 106 (61.5 %) clear cell renal cell carcinomas (ccRCCs), 35 (20 %) papillary renal cell carcinomas (pRCCs), and 32 (18.5 %) chromophobe renal cell carcinomas (ChRCCs), by immunohistochemistry on a tissue microarray. The association between expression of this marker and clinicopathologic parameters was then analysed.
  
  
  RESULTS
  There was a significant difference in the expression levels of CXCR4 in the ccRCC samples compared to the ChRCC and pRCC samples (P < 0.001). Increased expression of CXCR4 was significantly correlated with higher-grade tumours (P < 0.001) and worse stage (P = 0.001). A significant association was also found between expression of CXCR4 and microvascular invasion (P = 0.018). Among RCC subtypes, comparison of the differences between CXCR4 expression in low- and high-grade tumours demonstrated that pRCC tumours had a significantly higher expression of CXCR4 (P < 0.001) than ccRCC tumours (P = 0.01).
  
  
  CONCLUSIONS
  Significantly higher expression levels of CXCR4 were found in pRCC and ccRCC samples. Increased CXCR4 expression was associated with more aggressive tumour behaviour in RCC patients, especially in pRCC and ccRCC subtypes due to their more metastatic behaviour. These findings suggest that CXCR4 can be considered as a novel diagnostic and therapeutic marker for targeted therapy of renal carcinoma.
authors.affiliation: Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next to Milad Tower, Tehran, 14496-14530, Iran.
authors.forename: Arezoo
authors.initials: A
authors.lastname: Rasti
authors.affiliation: Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next to Milad Tower, Tehran, 14496-14530, Iran.|Hasheminejad Kidney Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Abolhasani
authors.affiliation: Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next to Milad Tower, Tehran, 14496-14530, Iran.
authors.forename: Leili Saeednejad
authors.initials: LS
authors.lastname: Zanjani
authors.affiliation: Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next to Milad Tower, Tehran, 14496-14530, Iran.|Hasheminejad Kidney Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Asgari
authors.affiliation: Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next to Milad Tower, Tehran, 14496-14530, Iran. mitmehr@yahoo.com.|Hasheminejad Kidney Center, Iran University of Medical Sciences (IUMS), Tehran, Iran. mitmehr@yahoo.com.
authors.forename: Mitra
authors.initials: M
authors.lastname: Mehrazma
authors.affiliation: Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next to Milad Tower, Tehran, 14496-14530, Iran. zahra.madjd@yahoo.com.|Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. zahra.madjd@yahoo.com.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Madjd
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells; D019718:Receptors, CXCR4 / Q000378:metabolism*; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4
keywords: CXCR4; Cancer stem cells (CSCs); Renal cell carcinoma (RCC); Tissue microarray (TMA)