Chromosome 17p13 deletion is associated with an aggressive tumor phenotype in clear cell renal cell carcinoma.

BACKGROUND: Deletions of 17p13 recurrently occur in renal cell carcinoma (RCC) but their prognostic role seems to be uncertain. METHODS: To determine prevalence, relationship with tumor phenotype, and patient prognosis, a tissue microarray containing samples from 1809 RCCs was evaluated using dual labeling fluorescence in situ hybridization (FISH) with 17p13 and chromosome 17 centromere probes. RESULTS: A 17p13 deletion was found in 72 of 1429 interpretable tumors. The frequency of 17p13 deletions varied greatly between RCC subtypes and was highest in chromophobe RCC (24/72; 33.3%). 17p13 deletions were also found in 35 (3.7%) of 946 clear cell RCC, 9 (4.3%) of 208 papillary RCC, 1 of 121 oncocytomas (0.8%), as well as in several rare cases of comprising 1 of 7 Xp11.2 translocation cancers, 1 of 3 collecting duct carcinomas, and 1 of 20 not otherwise specified (NOS) carcinomas. In clear cell carcinomas, 17p13 deletions revealed a strong and consistent association with higher Fuhrman, ISUP, and Thoenes grade (p < 0.0001 each), and linked to advanced tumor stage (p = 0.0168), large tumor diameter (p = 0.0004), distant metastases (p = 0.0077), cancer-specific survival (p = 0.0391), and recurrence-free survival (p = 0.0072). In multivariate analysis, 17p13 deletions showed in clear cell RCC a dependent prognostic role for established clinical-pathological parameters. CONCLUSION: 17p13 deletions have a dual role in RCC. They are associated with disease progression in clear cell RCC and possibly other subtypes and they are linked to the development of chromophobe RCC-a subtype with a particularly favorable prognosis.

Aberrant expression of membranous carbonic anhydrase IX (CAIX) is associated with unfavorable disease course in papillary and clear cell renal cell carcinoma.

OBJECTIVE: Antibodies against carbonic anhydrase IX (CAIX) are often part of immunohistochemical panels used to assist renal cell cancer (RCC) subtyping. This study was undertaken to determine, whether assessing CAIX expression levels could provide additional prognostic information. METHODS AND MATERIALS: More than 1,800 RCCs were analyzed in a tissue microarray (TMA) format for CAIX expression. All tumors had been reviewed and newly classified according to the WHO 2016 classification. RESULTS: Membranous CAIX expression revealed a "black and white" pattern that was strikingly dependent on the RCC subtype. In clear cell RCC, 89.2% of cancers showed strong positivity. The few clear cell RCC with lower CAIX expression levels were more likely to exhibit unfavorable tumor phenotype (p < 0.0001) and poor disease course (p = 0.0036). CAIX was completely absent in 99% of chromophobe RCC and in 100% of oncocytomas. In papillary RCC, 80.2% of cancers showed complete absence of CAIX staining. Papillary RCC with detectable CAIX expression had a less favorable tumor phenotype (p≤0.05) and worse disease outcome (p = 0.0176). These data are consistent with the concept, that "aberrant" CAIX staining - meaning absent or weak staining in a cancer expected to have a high level CAIX expression such as clear cell RCC or detectable CAIX expression in tumors that are typically CAIX negative such as papillary and chromophobe RCC - reflects biologic tumor dedifferentiation. CONCLUSION: Our data demonstrate that CAIX is a highly useful diagnostic biomarker for RCC providing both diagnostic and prognostic information.