Improved prediction of High ISUP Grade Clear Cell Renal Cell Carcinoma


Renal cell carcinoma (RCC) is one of the most common malignancies of the genitourinary system, and it constitutes 3% of adult malignant tumors and accounts for 2% of all cancer mortality. Clear cell RCC (ccRCC) is the predominant histological subtype of RCC, accounting for approximately 80% of cases.

Advanced ccRCCs are thought to be associated with a more aggressive clinical course and worse prognosis. The Fuhrman system was initially recommended as the histological grading system for RCC, but despite its wide use, it failed to take into consideration the latest histological subtypes of RCC, and was prone to poor interpretability and consequently poor inter-observer concordance regarding histopathological scoring. Therefore, the International Society of Urological Pathology (ISUP) Consensus Conference made recommendations, in an attempt to improve the prognostic value of these factors in the assessment of the various histomorphological phenotypes of RCC, by applying these recommendations, increased tumor grade was found to be associated with poor patient outcomes. Thus, the International Agency for Research on Cancer replaced the Fuhrman system with a new system based on the WHO/ISUP grading system.

Renal tumor biopsy plays an important role in the screening of candidates for personalized therapy and yet the sensitivity and accuracy of renal tumor biopsy analysis remains questionable, particularly for ccRCC, therefore the accuracy of diagnosis from renal tumor biopsy remains inadequate. Given the diagnostic inadequacies associated with preoperative biopsy in ccRCC, an increasing number of studies have attempted to incorporate more convenient clinical profiles and immunohistochemical or gene expression biomarkers to refine the ISUP grading system.

In a recent research paper published in journal, Frontiers in Oncology, Fudan University Shanghai Cancer Center led by Professor Ding-Wei Ye decided to investigate the value of integrating clinical profiles and immunohistochemical biomarkers in facilitating the diagnosis of high ISUP grade ccRCC. A total of 362 patients undergoing radical nephrectomy or nephron-sparing surgery in their institute were recruited for the study. The analysis obtained was used to construct a nomogram for the prediction of ISUP grade risk in ccRCC.

Their study consisted of two stages; the first stage involved an assessment of the associations between specific clinical or immunohistochemical markers and ISUP while the second stage consisted of a prognostic model comprising combined profiles was constructed and verified to predict high-grade risk using nomogram.

The authors observed when classifying the patients that patients with high ISUP grade were more likely to be older, have a larger maximal tumor diameter, be symptomatic, and to have undergone radical nephrectomy. Also it was observed that seven indicators were identified for predicting grade, these are age, tumor diameter, surgical method, CK7, Ki-67, PTEN, and mTOR expression.

Furthermore, the validation of the integrated score and nomogram in predicting high ISUP was achieved through studies in 121 ccRCC patients with fully recorded pre-operation surgical plans; it was observed that the AUC index was 0.791 which was similar to that of the training set. This confirms that the integrated score and nomogram demonstrate good performance in predicting ISUP grade.

Professor Ding-Wei Ye and his colleagues successfully developed an integrated nomogram comprising clinical and immunohistochemical indicators to predict high ISUP grade for ccRCC patients. This nomogram offers potentially useful information during preoperative risk assessment and may help urologists when evaluating personalized management regimens.


Improved prediction of High ISUP Grade Clear Cell Renal Cell Carcinoma

About the author

Prof. Dingwei Ye was vice president of the Fudan University Shanghai Cancer Center (FUSCC), chairman of genitourinary cancer committee of Chinese Anti-Cancer Association, vice president of Chinese Society of Clinical Oncology Kidney Cancer experts committee, Immunotherapy experts committee, and Chinese Anti-Cancer Association Family Hereditary Oncology group.

As a leading expert in genitourinary oncology, Prof. Ye has long been committee to the translational and clinical research of urinary tumors, especially malignancies. Prof. Ye has been granted 50 national and provincial foundations with more than 200 publications in high-impact SCI journals. He has been awarded more than 10 top prizes in China, including Wujieping Urology Medicine Prize which is awarded to most valuable urologist in China annually.

Prof. Ye established the multi-disciplinary team of genitourinary oncology in FUSCC. This team is a leading multi-disciplinary team internationally. Prof. Ye is chief of this team and is responsible for the overall operation. Co-corresponding authors of this study, Prof. Hai-liang Zhang and Dr. Yuan-yuan Qu are key members in this multi-disciplinary team, major in clinical and translational researches on kidney cancers. They all received PhD in oncology in Fudan University.

First author, Dr. Junlong Wu received M.D. degree from Fudan University in 2018 and started his career FUSCC, focusing on genetics and construction of molecular models in kidney malignancies. Co-first author, Wen-Hao Xu is a Master degree student in FUSCC and works on clinical research of renal cell carcinoma under the guidance of Prof. Dingwei Ye and Prof. Hai-Liang Zhang.



Wu, J., Xu, W., Wei, Y., Qu, Y., Zhang, H., Ye, D., An Integrated Score and Nomogram Combining Clinical and Immunohistochemistry Factors to Predict High ISUP Grade Clear Cell Renal Cell Carcinoma, Frontiers in Oncology(2018), doi: 10.3389/fonc.2018.00634

Go To Frontiers in Oncology(2018)