Oncotarget

Research Papers: Pathology:

Mutations of KRAS, NRAS, BRAF, EGFR, and PIK3CA genes in urachal carcinoma: Occurence and prognostic significance

Orsolya Módos, Henning Reis, Christian Niedworok, Herbert Rübben, Attila Szendröi, Marcell A. Szász, József Tímár, Kornélia Baghy, Ilona Kovalszky, Tomasz Golabek, Piotr Chlosta, Krzysztof Okon, Benoit Peyronnet, Romain Mathieu, Shahrokh F. Shariat, Péter Hollósi, Péter Nyirády and Tibor Szarvas _

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Oncotarget. 2016; 7:39293-39301. https://doi.org/10.18632/oncotarget.9828

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Abstract

Orsolya Módos1, Henning Reis2, Christian Niedworok3, Herbert Rübben3, Attila Szendröi1, Marcell A. Szász4, József Tímár4, Kornélia Baghy5, Ilona Kovalszky5, Tomasz Golabek6, Piotr Chlosta6, Krzysztof Okon7, Benoit Peyronnet8, Romain Mathieu8, Shahrokh F. Shariat9, Péter Hollósi5,10, Péter Nyirády1 and Tibor Szarvas1,3

1 Department of Urology, Semmelweis University, Budapest, Hungary

2 Institute of Pathology, University of Duisburg-Essen, Essen, Germany

3 Department of Urology, University of Duisburg-Essen, Essen, Germany

4 2nd Department of Pathology, Semmelweis University, Budapest, Hungary

5 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

6 Department of Urology, Jagiellonian University, Krakow, Poland

7 Department of Pathomorphology, Jagiellonian University, Krakow, Poland

8 Department of Urology, Rennes University Hospital, Rennes, France

9 Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria

10 Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary

Correspondence to:

Tibor Szarvas, email:

Keywords: urachal carcinoma, urachal cancer, urachus, mutation, EGFR, Pathology Section

Received: April 08, 2016 Accepted: May 29, 2016 Published: June 05, 2016

Abstract

Purpose: Targeted therapy represents an attractive alternative for rare tumors such as urachal carcinoma (UrC). The aim of this study was to assess the mutations of the most commonly affected 5 genes in the targetable EGFR-pathway in UrC and comapre their frequencies to those of found in urothelial and colorectal cancer.

Materials and Methods: Mutational hot-spots of selected genes were tested in 22 UrC samples by pyrosequencing. Mutational patterns were compared to those published for colorectal and urothelial cancers. Furthermore, we sought correlations between mutations and clinicopathological and follow-up data.

Results: We found 11 mutations in 10 of 22 (45%) patients. The most frequently mutated gene was KRAS (27%) followed by BRAF (18%) and NRAS (5%), while no mutations were detected in the EGFR and PIK3CA genes. No correlation was found between the mutation status and clinicopathological parameters (Sheldon/Mayo stage, tumor grade, metastases). Furthermore, none of the mutations correlated with progression-free or overall survival.

Conclusions: The mutation pattern of UrC is more similar to colorectal than to urothelial cancer. However, the mutation characteristics of UrC seems to be unique suggesting that clinical decision-making for UrC cannot be simply adopted from urothelial or colorectal carcinoma. The high occurence of EGFR-pathway mutations warrants the testing for KRAS and BRAF mutations when considering anti-EGFR therapy in UrC.


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