Significance of Chromosome 9p Status in Renal Cell Carcinoma: A Systematic Review and Quality of the Reported Studies

Abstract

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.

Metastatic renal cell carcinoma with undetectable renal mass presenting as lymphadenopathy

“…The positivity of expression of low molecular weight CAM 5.2, PAX 8, CD 10, vimentin, CAIX and RCC marker and the negativity of CK 7, CK 20, TTF1 and S100 highly supports the proposed diagnosis of mRCC [13,14]. The genomic alterations detected further favored the diagnosis; recent data implicated PBRM1 to be associated with clear cell RCC16 as well as alterations in CDKN2A [15][16][17]. Afterwards, upon reviewing numerous radiological images, no solid renal mass was detected.…”

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

“…However, the application of this genetic information has yet to progress to the clinical setting, and a few would question application of this information in healthcare. A recent systematic review [ 19 ] carried out to assess the quality of studies reporting the significance of 9p chromosomal abnormalities in RCC and to assess whether it could be used as a tool to predict oncological outcomes in RCC. Looking at 11 studies, including a total of 1431 patients, it was found that more work including standardization of techniques were needed to validate the clinical role of 9p status.…”

Tumour suppressor gene (CDKNA2) status on chromosome 9p in resected renal tissue improves prognosis of localised kidney cancer

“…A recent review of published literature on prognostic value of 9p deletion in RCC has shown that most studies were observational and used a wide variety of molecular and conventional cytogenetic techniques. The studies were mostly old series with no common protocols, which led to a discrepancy in the outcomes and the quality of the studies reviewed [ 4 ].…”