An Integrated Score and Nomogram Combining Clinical and Immunohistochemistry Factors to Predict High ISUP Grade Clear Cell Renal Cell Carcinoma

Abstract

Objective: The International Society of Urological Pathology (ISUP) has proposed a grading system to classify renal cell carcinoma (RCC). However, classification using biopsy specimens remains problematic and, consequently, the accuracy of a biopsy-based diagnosis is relatively poor. This study aims to combine clinical and immunohistochemical (IHC) factors for the prediction of high ISUP grade clear cell RCC (ccRCC) in an attempt to complement and improve the accuracy of a biopsy-based diagnosis.Methods: A total of 362 ccRCC patients were enrolled in this study and used for the training set. We performed IHC analysis of 18 protein markers on standard tissue sections using an automated stainer. Multivariate logistic regression models were developed to evaluate independent predictors for high ISUP grade. We evaluated different prediction models using receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) analysis. A nomogram for the derivation of an integrated score for predicting high ISUP grade ccRCC and a calibration curve were also plotted. Finally, an internal validation cohort was examined to evaluate the performance of our integrated scoring system and nomogram.Results: Multivariate logistic analyses revealed seven credible candidates for predicting high grade ISUP. These were age, tumor diameter, surgery, and CK7, Ki-67, PTEN, and MTOR protein expression. The ROC curves for the clinical, IHC and integrated models were compared in the training set, and the AUC for each was 0.731, 0.744, and 0.801, respectively. DeLong's test showed that the integrated model was significantly better at predicting high ISUP grade, when compared with the other models. Internal validation confirmed the good performance of the integrated score in predicting ISUP grade.Conclusion: We have developed a nomogram integrating clinical and immunohistochemical parameters to predict high ISUP grade for M0 ccRCC patients. This nomogram may offer potentially useful information during preoperative individualized patient risk assessment, and consequently may help urologists when planning personalized management regimens.

Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma

“…Clinical analysis showed that ccRCC patients with the PTEN mutation have a significantly poorer prognosis in survival and disease recurrence. All these results indicate the significance of the clinical practice of the PTEN mutation in ccRCC patients, consistent with some recent research (22, 23). The detection of tumor gene mutations has been applied to the clinic, which can help clinicians judge the prognosis of patients and effectively select better individualized treatment strategies.…”

Prognostic value and immune infiltration of novel signatures in clear cell renal cell carcinoma microenvironment

“…Bioinformatics analysis generates large and complex biological data through the comprehensive use of biology, computer science, and information technology. Its rapid development, such as The Cancer Genome Atlas (TCGA) database, provides researchers with a more user-friendly and convenient platform, guiding the implementation of basic experiments [12, 13]. In 2013, Yoshihara et al calculated specific molecular biomarker expression in immune and stromal cells, and thus generated an ESTIMATE algorithm with immune/stromal/ESTIMATE scores to predict the TME [9].…”

An immune scores-based nomogram for predicting overall survival in patients with clear cell renal cell carcinoma

“…[ 19 , 20 ] In recent years, many studies on the prognostic nomograms of ccRCC have been reported. [ 21 – 23 ] Also, a previous study has reported a predictive nomogram with immune-associated gene signature for ccRCC patients. [ 24 ] However, these studies on prognostic nomograms for ccRCC did not involve immune scores which can reflect the extent of immune cell infiltration.…”