Abstract
Fibrosis plays an important role in tumor growth and progression, and thus, we aimed to determine whether renal fibrosis is correlated with the clinical and pathological characteristics and prognosis of clear cell renal cell carcinoma (ccRCC). Fibrosis, including intra-tumoral fibrosis (ITF), pseudo-capsule (PC) fibrosis and adjacent normal renal interstitial fibrosis, was evaluated in 73 pairs of ccRCC specimens using second harmonic generation combined with two-photon excitation fluorescence (SHG/TPEF). The clinical and pathological characteristics of the patients who were eligible for the present study were recorded. The associations between fibrosis and clinicopathological parameters were analyzed using a Mann-Whitney U test or logistic regression analysis. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method and a Cox regression model. High-resolution images of fibrosis were captured from unstained slides using the SHG/TPEF approach. Both ITF and PC fibrosis were associated with tumor progression in ccRCC. Multivariate logistic regression analysis revealed a significant inverse association between the PC collagen proportional area (CPA) and PC invasion (p < 0.05), suggesting that PC CPA is an independent risk factor or marker for PC invasion. A significant decrease in progression-free survival (PFS), determined by Kaplan-Meier curves, was observed for patients with higher PC CPA status compared with those with lower PC CPA status (p < 0.05). Similar results were observed in patients with PC invasion. In multivariate Cox regression analysis, PC invasion and intra-tumoral necrosis were identified as independent prognostic factors for PFS. Our data suggest that ITF and PC fibrosis are associated with ccRCC progression. In addition, PC fibrosis may act as a marker of PC invasion and an effective quantitative measurement for assessing prognosis.
Highlights
Fibrotic responses are common characteristics of many malignancies, such as prostate cancer, breast cancer and pancreatic adenocarcinoma [1,2,3]
In Clear cell renal cell carcinoma (ccRCC), intra-tumoral fibrosis (ITF) was confirmed to be related to adverse pathological parameters, such as Fuhrman nuclear grade, intra-tumoral necrosis and inflammation, but ITF itself did not have prognostic significance [5]; whether ITF can serve as an indicator of immune status and prognosis in ccRCC should be explored
These results demonstrate the possibility that ITF was destroyed in the process of ccRCC progression, indicating a decreased barrier for cancer cell motility
Summary
Fibrotic responses are common characteristics of many malignancies, such as prostate cancer, breast cancer and pancreatic adenocarcinoma [1,2,3]. Diagnostics 2020, 10, 895 fibrosis might serve as an indicator of the different immune statuses of a malignancy. Clear cell renal cell carcinoma (ccRCC) is the most common phenotype of renal cell carcinoma (RCC), which is derived from renal tubule epithelial cells and is often characterized by intra-tumoral fibrosis (ITF) and peritumoral pseudo-capsules (PCs). ITF is associated with tumor type and lower lymphocytic infiltration. ITF has been identified as having prognostic implications and is correlated with intra-tumoral necrosis and inflammation [4]. In ccRCC, ITF was confirmed to be related to adverse pathological parameters, such as Fuhrman nuclear grade, intra-tumoral necrosis and inflammation, but ITF itself did not have prognostic significance [5]; whether ITF can serve as an indicator of immune status and prognosis in ccRCC should be explored
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