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

Abstract

Introduction:The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC) is evolving, and Carbonic Anhydrase type IX (CA-IX) has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1) overall survival, and 2) with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion). Materials and Methods: This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS), TNM stage, tumor size (TS), Fuhrman nuclear grade (FNG), microvascular invasion (MVI), peri-renal fat invasion (PFI). We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: The mean follow-up time was 7.9 years (range 1.9 to 19.5 years).The analysis of CA-IX expression against the selected prognostic parameters showed no correlation.

hERG1 and CA IX expression are associated with disease recurrence in surgically resected clear cell renal carcinoma

“…We did not find association between CA IX and prognosis for ccRCC patients, in accordance with other studies such as the one by Zerati and colleagues [29] although it is worth recalling that they evaluated overall survival instead of recurrence and cancer specific survival, as in our study.…”

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 .…”

“…Recent large cohort studies with long-term follow up found that CAIX is not an independent prognostic marker for renal carcinoma [18], [19].…”

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2

“…They failed to find a correlation between CA9 expression, tumor stage and grade, yet observed that tumors with low CA9 expression behave in a considerably more aggressive fashion and this effect was evident also in multivariate analysis. On the other hand, some of the most recent papers have failed to show the prognostic significance of CA9 [20,21]. Zerati et al [20] analyzed a group of non-metastatic RCCs, and found no relationship between CA9 and overall survival, tumor stage, size, invasiveness or vascular invasion.…”

“…On the other hand, some of the most recent papers have failed to show the prognostic significance of CA9 [20,21]. Zerati et al [20] analyzed a group of non-metastatic RCCs, and found no relationship between CA9 and overall survival, tumor stage, size, invasiveness or vascular invasion. Zhang et al [21] analyzed a large cohort of RCC cases with periods of observation exceeding 10 years.…”