Urachal carcinoma: from gross specimen to morphologic, immunohistochemical, and molecular analysis

Riva, Giulio; Mian, Christine; Luchini, Claudio; Girolami, Ilaria; Ghimenton, Claudio; Cima, Luca; Novelli, Luca; Hanspeter, Esther; Mazzoleni, Guido; Schwienbacher, Christine; Pycha, Stefan; D’Elia, Carolina; Trenti, Emanuela; Pycha, Armin; Martignoni, Guido; Hes, Ondřej; Eccher, Albino; Nesi, Gabriella; Brunelli, Matteo

doi:10.1007/s00428-018-2467-1

Cited by 20 publications

(19 citation statements)

References 40 publications

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“…Summarizing our results with all currently available data on APC status in UrC, an overall number of 14 of 141 (10%) UrC samples exhibited APC alterations [ 6 – 16 , 18 , 24 – 26 ] which is in clear contrast to the high APC mutational rate (80%) found in CRC [ 17 ]. This finding represents a further characteristic difference in the molecular taxonomy between CRC and UrC.…”

Section: Discussionsupporting

confidence: 73%

“…In contrast to CRC, the molecular background of UrC is only poorly understood. Data on UrC’s mutational pattern further highlighted its similarity to CRC with overlapping mutational patterns such as in TP53 , KRAS , SMAD4 and NRAS [ 6 – 17 ]. On the other hand, later studies also identified some significant molecular differences between UrC and CRC [ 6 – 12 , 14 – 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Prevalence of APC and PTEN Alterations in Urachal Cancer

Nagy

Reis

Hadaschik

et al. 2020

Pathol. Oncol. Res.

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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.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Prevalence of APC and PTEN Alterations in Urachal Cancer

Nagy

Reis

Hadaschik

et al. 2020

Pathol. Oncol. Res.

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“…For UAC, several studies have been published which mainly focus on current therapeutic targets [11][12][13][14][15][16]. Reis et al identified, for instance, various druggable alterations (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…So far, the pathogenesis of BAC remains poorly understood, and morphological resemblance to colorectal adenocarcinomas (CORAD) suggests potential analogies. Nextgeneration sequencing (NGS) data have improved our knowledge of genetic driver alterations in urothelial carcinomas [7] and CORAD [8], and first NGS data are now available for rare BAC [9,10] and UAC [11][12][13][14][15][16]. Additionally, a few single gene sequencing reports for BAC and UAC (e.g.…”

Section: Introductionmentioning

confidence: 99%

Comparative genomic profiling of glandular bladder tumours

et al. 2020

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Primary glandular bladder tumours (bladder adenocarcinoma [BAC], urachal adenocarcinoma [UAC], urothelial carcinoma with glandular differentiation [UCg]) are rare malignancies with histological resemblance to colorectal adenocarcinoma (CORAD) in the majority of this subgroup. Definite case numbers are very low, molecular data are limited and the pathogenesis remains poorly understood. Therefore, this study was designed to complement current knowledge by in depth analysis of BAC (n = 12), UAC (n = 13), UCg (n = 11) and non-invasive glandular lesions (n = 19). In BAC, in addition to known alterations in TP53, Wnt, MAP kinase and MTOR pathway, mutations in SMAD4, ARID1A and BRAF were identified. Compared to published data on muscle invasive bladder cancer (BLCA) and CORAD, UCg exhibited frequent "urothelial" like alterations while BAC and UAC were characterised by a more "colorectal" like mutational pattern. Immunohistochemically, there was no evidence of DNA mismatch repair deficiency or PD-L1 tumour cell positivity in any sample. Depending on the used antibody 0-45% of BAC, 0-30% of UCg and 0% UAC cases exhibited PD-L1 expressing tumour associated immune cells. A single BAC (9%, 1/11) showed evidence of ARID1A protein loss, and two cases of UCg (20%, 2/10) showed loss of SMARCA1 and PBRM1, respectively. Taken together, our data suggest at least in part involvement of similar pathways driving tumourigenesis of adenocarcinomas like BAC, UAC and CORAD independent of their tissue origin. Alterations of TERT and FBXW7 in single cases of intestinal metaplasia further point towards a possible precancerous character in line with previous reports.

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“…The CEUS was able to better define lesion margins, bladder and abdominal wall infiltration. However, more than 80% urachus carcinomas are adenocarcinoma of the mucinous type and the mucin content of the tumors can explain the irregular enhancement at CEUS [17,18].…”

Section: Discussionmentioning

confidence: 99%

Ultrasound findings of urachal anomalies. A series of interesting cases

Luo

Lin

et al. 2019

Med Ultrason

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Aims: This study’s aim is to present the specific ultrasonography (US) findings of a series of urachus anomalies. Material and methods: Seven patients with suspected urachal anomalies underwent US scanning initially prior to the surgery and the features of images were reviewed respectively. The clinical data and pathologic results were collected also. Results: US successfully diagnosed urachal anomalies in 5 patients (5/7, 71.4%) and failed to diagnose in 2 patients (2/7, 28.6%). Patent urachus showed a tubule between the umbilicus and bladder; urachal sinus was a blind focal dilatation at the umbilical end, while vesicourachal diverticulum was an outpouching at the vesical end and urachal cyst was identified as an anechoic structure along the urachus. Non-enhancement in the base and centre was the distinct features of urachus carcinoma by contrastenhanced ultrasonography (CEUS). Using a high frequency probe and CEUS the diagnostic ability of US may be improved. Conclusion: US showed good diagnostic ability in urachal anomalies and combined with CEUS could improve the differential diagnosis.

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Urachal carcinoma: from gross specimen to morphologic, immunohistochemical, and molecular analysis

Cited by 20 publications

References 40 publications

Prevalence of APC and PTEN Alterations in Urachal Cancer

Prevalence of APC and PTEN Alterations in Urachal Cancer

Comparative genomic profiling of glandular bladder tumours

Ultrasound findings of urachal anomalies. A series of interesting cases

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