Abstract
Urachal carcinoma (UrC) is a rare tumor with remarkable histological and molecular similarities to colorectal cancer (CRC). Adenomatous polyposis coli (APC) is the most frequently affected gene in CRC, but the prevalence and significance of its alterations in UrC is poorly understood. In addition, loss of phosphatase and tensin homologue (PTEN) was shown to be associated with therapy resistance in CRC. Our primary aim was to assess specific genetic alterations including APC and PTEN in a large series of UrC samples in order to identify clinically significant genomic alterations. We analyzed a total of 40 UrC cases. Targeted 5-gene (APC, PTEN, DICER1, PRKAR1A, TSHR, WRN) panel sequencing was performed on the Illumina MiSeq platform (n = 34). In addition, ß-catenin (n = 38) and PTEN (n = 30) expressions were assessed by immunohistochemistry. APC and PTEN genes were affected in 15% (5/34) and 6% (2/34) of cases. Two of five APC alterations (p.Y1075*, p.K1199*) were truncating pathogenic mutations. One of the two PTEN variants was a pathogenic frameshift insertion (p.C211fs). In 29% (11/38) of samples, at least some weak nuclear ß-catenin immunostaining was detected and PTEN loss was observed in 20% (6/30) of samples. The low prevalence of APC mutations in UrC represents a characteristic difference to CRC. Based on APC and ß-catenin results, the Wnt pathway seems to be rarely affected in UrC. Considering the formerly described involvement of PTEN protein loss in anti-EGFR therapy-resistance its immunohistochemical testing may have therapeutic relevance.
Highlights
The urachus is an extraperitoneal fibromuscular band that connects the bladder dome and the umbilicus
Formalin-fixed paraffin embedded (FFPE) tumor tissues from 40 urachal adenocarcinoma patients were retrospectively collected from nine academic centers
The most frequent symptom of urachal cancer (UrC) was haematuria reported in 83% of patients
Summary
The urachus is an extraperitoneal fibromuscular band that connects the bladder dome and the umbilicus. After the fourth month of embryonic life, the urachus usually transforms into a fibromuscular strand (i.e. median umbilical ligament). Incomplete regression of the urachal structure may lead to various diseases including urachal cancer (UrC) [1, 2]. Because of its hidden anatomical location, UrC is mostly detected in progressed stages when patients present with hematuria resulting from its invasion into the urinary bladder. At this advanced stage, the overall 5-year survival is only about 50% [3,4,5]
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