title: Neutrophil gelatinase-associated lipocalin immunoexpression in renal tumors: correlation with histotype and histological grade.
abstract: Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein with roles in iron trafficking as well as in carcinogenesis and progression of several human neoplasias. Although the renal proximal tubule represents a major source of NGAL synthesis under various injurious stimuli to the kidney, NGAL expression has been rarely evaluated in renal tumors up to now. In view of this, in the present study we analyzed the expression of this protein in renal tumors of different histotype and grade so as to evaluate whether a role for NGAL might be also proposed in the carcinogenesis of these neoplasms. NGAL immunoexpression was analyzed in 30 surgically resected renal tumors [18 clear cell, 5 papillary and 3 chromophobe renal cell carcinomas (RCCs), 2 urothelial carcinomas and 2 oncocytomas] and in the peritoneal metastasis of a clear cell RCC. A variable NGAL immunoexpression was found in 28/30 cases. High NGAL expression was significantly associated with the papillary and chromphobe histotypes (P=0.016) and with a higher histological grade of clear cell and papillary RCC (P=0.004). Moreover, NGAL expression was retained in the peritoneal metastasis of clear cell RCC. Our findings demonstrate that NGAL is expressed in several histotypes of renal tumors. Its highest expression in the papillary and chromophobe histotypes might be related to a higher need in iron uptake, which could be exploited in anti-cancer therapies with iron chelators against these neoplasias. Further studies are required to investigate the potential diagnostic utility of NGAL in the early diagnosis of metastatic progression of RCC.
authors.affiliation: Departments of Human Pathology, University of Messina, Messina, Italy. vbarresi@unime.it
authors.forename: Valeria
authors.initials: V
authors.lastname: Barresi
authors.forename: Antonio
authors.initials: A
authors.lastname: Ieni
authors.forename: Davide
authors.initials: D
authors.lastname: Bolignano
authors.forename: Carlo
authors.initials: C
authors.lastname: Magno
authors.forename: Michele
authors.initials: M
authors.lastname: Buemi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Barresi
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000145:classification / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000145:classification / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000556:secondary; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins