Collecting Duct Carcinomas Represent a Unique Tumor Entity Based on Genetic Alterations

Abstract

Collecting duct carcinoma (CDC) is a rare renal neoplasm that is associated with poor prognosis due to its highly aggressive course and limited response to immuno- or chemotherapy. Histologically, CDC is defined as a subtype of renal cell carcinomas, but in some cases, it is difficult to differentiate from urothelial carcinomas (UC). Therefore the aim of this study was to determine genetic alterations of CDC in comparison to that of urothelial carcinomas of the upper urinary tract (UUT-UC) to clarify the histological origin of this rare tumor entity. Twenty-nine CDC samples were obtained from seven different German centers and compared with twenty-six urothelial carcinomas of the upper urinary tract. Comparative genomic hybridization (CGH) was used to investigate the genetic composition of patients’ tumors and allowed the detection of losses and gains of DNA copy numbers throughout the entire genome. The clinical data were correlated with CGH results. CGH analysis of CDC revealed DNA aberrations in many chromosomes. DNA losses were more frequently observed than gains, while high-level amplifications were not detected. The mean frequency of CDC chromosomal aberrations (4.9/case) was slightly lower than that in UUT-UC (5.4/case). Recurrent CDC DNA losses occurred at 8p (n=9/29), 16p (9/29), 1p (n=7/29) and 9p (n=7/29), and gains occurred in 13q (n=9/29). In contrast to CDC, the most frequently detected UUT-UC DNA aberration was a loss at 9q (n=13/26). DNA losses at 9q, 13q and 8q as well as gains at 8p showed significant variations in UUT-UC compared to CDC. There was no correlation between the patients’ clinical course and the presence or absence of these recurrent genetic alterations. CDCs are characterized by a different genetic pattern compared to UUT-UC. Regarding the published data on renal cell carcinoma, we conclude that CDC appears to be a unique entity among kidney carcinomas.

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

“…Collecting duct carcinoma (CDC) or Bellini duct carcinoma remains a highly aggressive RCC arising from the renal collecting tubules. A recent specific gene expression signature showed that CDC appears to be a unique entity among kidney cancers [11]. Moreover, these tumours are characterised by an immune profile with an average of 22% of tumour-infiltrating lymphocytes [12].…”

High grade infiltrative adenocarcinomas of renal cell origin: New insights into classification, morphology, and molecular pathogenesis

“…Perhaps most interestingly, the patterns of gene expression in CDC were most like those of the distal convoluted tubules of the nephron, providing support for the hypothesis of origin in the distal nephron. The question of molecular overlap with upper tract urothelial carcinoma has also been addressed from the standpoint of CGH, where substantially different recurrent DNA losses and gains were observed in CDC compared to urothelial carcinoma . We note the caveat in all of these results that it is unclear whether or how FH‐deficient carcinoma was excluded from the CDC cases studied.…”

“…The question of molecular overlap with upper tract urothelial carcinoma has also been addressed from the standpoint of CGH, where substantially different recurrent DNA losses and gains were observed in CDC compared to urothelial carcinoma. 79 We note the caveat in all of these results that it is unclear whether or how FH-deficient carcinoma was excluded from the CDC cases studied. Indeed two of the CDCs in the latter CGH study 79 seem to have harbored (albeit broad) chromosomal losses involving the area of the FH locus.…”

“…We note the caveat in all of these results that it is unclear whether or how FH‐deficient carcinoma was excluded from the CDC cases studied. Indeed two of the CDCs in the latter CGH study seem to have harbored (albeit broad) chromosomal losses involving the area of the FH locus.…”

Renal cell carcinoma: Review of etiology, pathophysiology and risk factors

“…Associated chromosomal abnormalities are losses of various chromosomal regions on chromosomes: -1p, -8p, -9p, and gains on chromosome at-13q (ref. 34 ).…”