[893] KRAS Is Mutated in a Subset of Mucinous Type Urachal Adenocarcinomas (UAC)

Lloyd Hutchinson, Gladell P Paner, Keith Tomaszewicz, Vikas Mehta, Sahussapont Joseph Sirintrapun, Guliz A Barkan, Ediz F Cosar. University of Massachusetts, Worcester, MA; Loyola University Medical Center, Maywood, IL; Wake Forest University, Winston Salem, NC; University of Chicago, Chicago, IL

Background: Activating mutations in KRAS and BRAF are frequently found in sporadic colorectal adenocarcinoma (CAC), and are established therapeutic markers. Mutations in KRAS can also occur in other organ adenocarcinomas such as lung and pancreas, particularly in mucinous type. The rare UAC has several morphological types that include intestinal, mucinous, signet ring cell, and other types. The intestinal UAC has striking morphologic and immunohistochemical overlap with CAC. To date, the mutational status of KRAS and BRAF in UAC has not been investigated.
Design: Twelve UACs (8 mucinous, 2 enteric, 1 signet ring cell, and 1 not otherwise specified [NOS] types) were included in the study. KRAS mutation analysis for codons 12 and 13 of the KRAS oncogene and BRAF mutation analysis for known mutations between codons 598 and 602 including the V600E mutation of the BRAF oncogene were performed.
Results: KRAS mutations were detected in 4/8 (50%) of mucinous type UAC (table). Mutations were all in codon 12 and included 2 glycine to aspartate (p.G12D), 1 glycine to thymine (p.G12C) and 1 glycine to aspartate (p.G12S). No KRAS mutation was detected in other morphologic types. No BRAF mutation was detected in all UAC analyzed.

AUC typesKRASBRAF
MucinousPositive (p.G12D)Negative
MucinousPositive (p.G12D)Negative
MucinousPositive (p.G12C)Negative
MucinousPositive (p.G12S)Negative
MucinousNegativeNegative
MucinousNegativeNegative
MucinousNegativeNegative
MucinousNegativeNegative
EntericNegativeNegative
EntericNegativeNegative
Signet ring cellNegativeNegative
NOSNegativeNegative



Conclusions: Mutations in KRAS are present in a subset of mucinous type UAC and may play a role in the oncogenesis of urachal mucinous tumors. Currently, there is no standardized chemotherapeutic regimen for UAC, and in some instances UAC patients received CAC regimens. Future drug trials such as those that targets epidermal growth factor receptor (EGFR) similar to those in CAC may perhaps uncover the clinical relevance of KRAS mutation in UAC.
Category: Genitourinary (including renal tumors)

Tuesday, March 20, 2012 1:15 PM

Platform Session: Section A, Tuesday Afternoon

 

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