Microsatellite alteration and immunohistochemical expression profile of chromosome 9p21 in patients with sporadic renal cell carcinoma following surgical resection

BMC Cancer

Research Article

Ismail El-Mokadem¹  Ghulam Nabi¹  Alison Lim¹  Norman Pratt²  David Batty²  Stewart Fleming³  Katherine Garret³  Thomas Kidd³ 

[1] Academic Section of Urology, Division of Cancer Research, Ninewells Hospital, University of Dundee, DD1 9SY, Dundee, UK;Department of Cytogenetic, Ninewells Hospital, University of Dundee, DD1 9SY, Dundee, UK;Department of Pathology, Ninewells Hospital, University of Dundee, DD1 9SY, Dundee, UK;

关键词: Kidney cancer;    Genetics;    Microsatellite analysis;    Chromosome 9p;   

DOI  :  10.1186/s12885-016-2514-8

 received in 2015-07-22, accepted in 2016-06-27,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundLong-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.MethodsDNA 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.ResultsThe 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.ConclusionsLoss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on long-term follow-up.

【 授权许可】

CC BY   
© The Author(s). 2016