Significance of chromosome 9p status in renal cell carcinoma:a systematic review and quality of the reported studies

Defining the prognosis of renal cell carcinoma (RCC) using genetic tests is an evolving area. The prognostic significance of 9p status in RCC, although described in the literature, remains underutilised in clinical practice. The study explored the causes of this translational gap. A systematic review on the significance of 9p status in RCC was performed to assess its clinical applicability and impact on clinical decision-making. Medline, Embase, and other electronic searches were made for studies reporting on 9p status in RCC. We collected data on: genetic techniques, pathological parameters, clinical outcomes, and completeness of follow-up assessment. Eleven studies reporting on 1,431 patients using different genetic techniques were included. The most commonly used genetic technique for the assessment of 9p status in RCC was fluorescence in situ hybridization. Combined genomic hybridisation (CGH), microsatellite analysis, karyotyping, and sequencing were other reported techniques. Various thresholds and cut-off values were used for the diagnosis of 9p deletion in different studies. Standardization, interobserver agreement, and consensus on the interpretation of test remained poor. The studies lacked validation and had high risk of bias and poor clinical applicability as assessed by two independent reviewers using a modified quality assessment tool. Further protocol driven studies with standardised methodology including use of appropriate positive and negative controls, assessment of interobserver variations, and evidenced based follow-up protocols are needed to clarify the role of 9p status in predicting oncological outcomes in renal cell cancer

Case report of ureteric transection of lower moiety in high-speed road traffic collision

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Carcinoma in situ is significantly underdetected by prenephroureterectomy ureteroscopy in the management of upper tract urothelial cancers

Objective. Diagnostic reliability of prenephroureterectomy ureteroscopy (PNU) for the detection of upper tract carcinoma in situ (CIS) remains unproven in particular and underreported in general. Methods. Patients who underwent radical nephroureterectomy (RNU) in a large multicentre retrospective study for upper tract transitional cell carcinoma (UT-TCC) between January 2002 and December 2013 were identified from our hospitals databases. PNU appearances, stage, and grade of ureteroscopic biopsy were compared with final histology results of RNU to assess the diagnostic reliability of PNU for carcinoma in situ (CIS). Results. Three hundred patients underwent RNU for UT-TCC. 106 (106/300; 35.3%) of the cohort had PNU using white light with biopsies taken in most (92/106; 86.7%). Postnephroureterectomy histology of the cohort showed CIS in 65 (65/300; 21.6%) patients. Thirty nine of patients with CIS (39/65; 60%) had prenephroureterectomy ureteroscopy biopsies. Out of ten patients with CIS on ureteroscopic biopsies, six did not show CIS on final histopathology (6/10; 60%). Moreover, grading and staging on PNU biopsies of obvious tumours showed a significant nonconcordance with final histopathology of RNU specimen (P=0.02). Overall survival was also shorter in patients with CIS compared with those without; this showed strong statistical significance (P=0.004). Conclusions. There is a high incidence of CIS in upper tract with significant underdetection and discordance rate between the histopathology of biopsy samples obtained by white light PNU and resected specimen of radical nephroureterectomy. The presence of concomitant CIS and high stage disease in the upper tract TCC carried a poor prognosis following radical nephroureterectomy

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Loss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on long-term follow-up. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2514-8) contains supplementary material, which is available to authorized users