Tumor heterogeneity evaluated by computed tomography detects muscle-invasive upper tract urothelial carcinoma that is associated with inflammatory tumor microenvironment

Abstract

Abstract To detect muscle-invasive upper tract urothelial carcinoma, we evaluated the internal texture of the tumor using texture analysis of computed tomography images in 86 cases of upper tract urothelial carcinoma. The internal texture of the tumor was evaluated as the value of computed tomography attenuation number of the unenhanced image, and the median, standard deviation, skewness and kurtosis were calculated. Each parameter was compared with clinicopathological factors, and their associations with postoperative prognosis were investigated. Immunohistochemistry was performed to investigate the histological and molecular mechanisms of the inflammatory tumor microenvironment. The histogram of computed tomography attenuation number in non-muscle invasive tumor was single-peaked, whereas muscle invasive tumor showed a multi-peaked shape. In the parameters obtained by texture analysis, standard deviation was significantly associated with pathological stage (p < 0.0001), tumor grade (p = 0.0053), lymphovascular invasion (p = 0.0078) and concomitant carcinoma in situ (p = 0.0177) along with recurrence-free (p = 0.0191) and overall survival (p = 0.0184). The standard deviation value correlated with the amount of stromal components (p < 0.0001) and number of tumor-infiltrating macrophages (p < 0.0001). In addition, higher expression of high mobility group box 1 was found in heterogeneous tumor. Tumor heterogeneity evaluated by texture analysis was associated with muscle-invasive upper tract urothelial carcinoma and represented an inflammatory tumor microenvironment and useful as the clinical assessment to differentiate muscle invasive tumor.