title: Microsatellite alteration and immunohistochemical expression profile of chromosome 9p21 in patients with sporadic renal cell carcinoma following surgical resection.
abstract: Long-term prognostic significance of loss of heterozygosity on chromosome 9p21 for localized renal cell carcinoma following surgery remains unreported. The study assessed the frequency of deletions of different loci of chromosome 9p along with immunohistochemical profile of proteins in surgically resected renal cancer tissue and correlated this with long-term outcomes.
  
  
  
  DNA was extracted from renal tumours and corresponding normal kidney tissues in prospectively collected samples of 108 patients who underwent surgical resection for clinically localized disease between January 2001 and December 2005, providing a minimum of 9 years follow-up for each participant. After checking quality of DNA, amplified by PCR, loss of heterozygosity (LOH) on chromosome 9p was assessed using 6 microsatellite markers in 77 clear cell carcinoma. Only 5 of the markers showed LOH (D9S1814, D9S916, D9S974, D9S942, and D9S171). Protein expression of p15(INK4b), p16(INK4a), p14(ARF), CAIX, and adipose related protein (ADFP) were demonstrated by immunostaining in normal and cancer tissues. Loss of heterozygosity for microsatellite analysis was correlated with tumour characteristics, recurrence free, cancer specific, and overall survival, including significance of immunohistochemical profile of protein expressions.
  
  
  
  The main deletion was found at loci telomeric to CDKN2A region at D9S916. There was a significant correlation between frequency of LOH stage (p = 0.005) and metastases (p = 0.006) suggesting a higher LOH for advanced and aggressive renal cell carcinoma. Most commonly observed LOH in the 3 markers: D9S916, D9S974, and D9S942 were associated with poor survival, and were statistically significant on multivariate analysis. Immunohistochemical expression of p14, p15, and p16 proteins were either low or absent in cancer tissue compared to normal.
  
  
  
  Loss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on long-term follow-up.
authors.affiliation: Academic Section of Urology, Division of Cancer Research, Ninewells Hospital, University of Dundee, Dundee, DD1 9SY, UK.
authors.forename: Ismail
authors.initials: I
authors.lastname: El-Mokadem
authors.affiliation: Academic Section of Urology, Division of Cancer Research, Ninewells Hospital, University of Dundee, Dundee, DD1 9SY, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Lim
authors.affiliation: Department of Pathology, Ninewells Hospital, University of Dundee, Dundee, DD1 9SY, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kidd
authors.affiliation: Department of Pathology, Ninewells Hospital, University of Dundee, Dundee, DD1 9SY, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Garret
authors.affiliation: Department of Cytogenetic, Ninewells Hospital, University of Dundee, Dundee, DD1 9SY, UK.
authors.forename: Norman
authors.initials: N
authors.lastname: Pratt
authors.affiliation: Department of Cytogenetic, Ninewells Hospital, University of Dundee, Dundee, DD1 9SY, UK.
authors.forename: David
authors.initials: D
authors.lastname: Batty
authors.affiliation: Department of Pathology, Ninewells Hospital, University of Dundee, Dundee, DD1 9SY, UK.
authors.forename: Stewart
authors.initials: S
authors.lastname: Fleming
authors.affiliation: Academic Section of Urology, Division of Cancer Research, Ninewells Hospital, University of Dundee, Dundee, DD1 9SY, UK. g.nabi@dundee.ac.uk.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Nabi
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C401561:CDK2AP2 protein, human; C000614131:CDKN2A protein, human; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D015513:Oncogene Proteins
keywords: Chromosome 9p; Genetics; Kidney cancer; Microsatellite analysis