CA9 Expression as a Prognostic Factor in Renal Clear Cell Carcinoma

Abstract

Introduction: We investigated whether CA9 protein could be used as a prognostic tumor marker as well as a diagnostic biomarker in renal clear cell carcinoma. Materials and Methods: Nephrectomy specimens from 92 patients were used in this study. 80 of these were renal cell carcinomas, 10 adenomas and 2 oncocytomas. Of the renal cell carcinomas, 67 were clear cell carcinomas. Immunohistochemical analysis using CA9 monoclonal antibody (M75) was performed on paraffin-embedded specimens. CA9 staining was correlated with tumor stage, grade, lymph node involvement, distant metastasis and cumulative survival time. Results: CA9 was present in 91.2% of clear cell carcinomas. Low staining was a poor prognostic factor, and conversely high staining a good prognostic one. CA9 expression was found to be the best prognostic factor when compared with T stage and grade. Even in low-grade and stage tumors, the presence of low expression correlated with lowered survival times. Conclusions: On the basis of our study, CA9 is a significant molecular marker in renal clear cell carcinomas. Decreased CA9 expression is independently associated with poor survival. CA9 can be used to predict clinical outcome and identify high-risk patients in need for adjuvant immunotherapy and CA9 targeted therapies.

Prognostic Value of Carbonic Anhydrase IX Immunohistochemical Expression in Renal Cell Carcinoma: A Meta-Analysis of the Literature

“…After carefully review of each of the 50 studies, certain studies were excluded for the following rationale: six studies evaluated CAIX status by enzyme-linked immunosorbent assay (ELISA) [23], [24], [25], [26], [27], [28]; five studies evaluated CAIX status by real-time-PCR [29], [30], [31], [32], [33]; one study was on the topic of a single nucleotide polymorphism in the CAIX gene [34]; fourteen studies did not report survival outcome on CAIX expression or survival outcome could not be extracted [17], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47]; and nine studies contained overlapping data with other studies by the same authors or institutions [48], [49], [50], [51], [52], [53], [54], [55], [56]. Thus, fifteen papers were included in our meta-analysis to evaluate the relationship between CAIX expression and prognosis in patients with renal cell carcinoma [16], [18], [19], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68]. The selection process is shown in Figure 1 .…”

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

“…In the setting of metastatic RCC, the role of CA-IX is established, and there are many papers published in the literature reporting its usefulness as a predictor of survival, prognosis, and therapeutic response (11,(38)(39)(40)(41).…”

Molecular characterization of clonal human renal forming cells

“…Recent single cell RNA-seq of clear cell RCC disclosed a proximal tubular genetic signature with specifically elevated SLC17A3 and VCAM1. These molecules were overexpressed in FL clones along with ITGA5, GGT1, CDH6 and CA9 also previously shown to be highly expressed by clear cell RCC [33-37]. Thus, intriguingly proximal clonal proliferation shares markers of clear cell RCC.…”