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


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.
Department of Urology, Semmelweis University, Budapest, Hungary.
Orsolya
O
Módos
Institute of Pathology, University of Duisburg-Essen, Essen, Germany.
Henning
H
Reis
Department of Urology, University of Duisburg-Essen, Essen, Germany.
Christian
C
Niedworok
Department of Urology, University of Duisburg-Essen, Essen, Germany.
Herbert
H
Rübben
Department of Urology, Semmelweis University, Budapest, Hungary.
Attila
A
Szendröi
2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
Marcell A
MA
Szász
2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
József
J
Tímár
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Kornélia
K
Baghy
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Ilona
I
Kovalszky
Department of Urology, Jagiellonian University, Krakow, Poland.
Tomasz
T
Golabek
Department of Urology, Jagiellonian University, Krakow, Poland.
Piotr
P
Chlosta
Department of Pathomorphology, Jagiellonian University, Krakow, Poland.
Krzysztof
K
Okon
Department of Urology, Rennes University Hospital, Rennes, France.
Benoit
B
Peyronnet
Department of Urology, Rennes University Hospital, Rennes, France.
Romain
R
Mathieu
Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
Shahrokh F
SF
Shariat
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.|Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary.
Péter
P
Hollósi
Department of Urology, Semmelweis University, Budapest, Hungary.
Péter
P
Nyirády
Department of Urology, Semmelweis University, Budapest, Hungary.|Department of Urology, University of Duisburg-Essen, Essen, Germany.
Tibor
T
Szarvas
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D019459:Urothelium / Q000473:pathology
C117307:KRAS protein, human; D008565:Membrane Proteins; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
EGFR; Pathology Section; mutation; urachal cancer; urachal carcinoma; urachus