Urachal Adenocarcinoma Is Associated with Microsatellite Instability and KRAS Mutations
Adela Cimic, Joseph Sirintrapun, Jennifer Woo. Wake Forest University, Winston Salem, NC
Background: Urachal adenocarcinoma (UAC) is a rare tumor of the urinary bladder which can show intestinal, mucinous, and signet-ring cell (SRC) histology. The morphology is similar to that of colorectal adenocarcinoma (CAC). With mucinous and SRC morphology in CAC, the association is more with microsatellite instability (MSI). KRAS activating mutations are frequently seen in sporadic CAC, while BRAF has been reported in both sporadic and a subset with MSI. What is not known is whether UAC in its morphologic similarity to CAC can show immunohistochemical features of MSI along with KRAS and BRAF activating mutations.
Design: All cases of UAC (n=7) from our institution were selected. Analysis included 1) immunohistochemistry for microsatellite markers (MLH1, MSH2, MSH6, and PMS2), 2) KRAS mutation analysis for codons 12 and 13 of the KRAS gene, and 3) BRAF mutation analysis for codon 600 of the BRAF gene.
Results: All cases were adenocarcinoma. Six showed mucinous (muc) histology with four of those with additional signet-ring cell (SRC) histology. Two of those four cases had focal (f) SRC presence. Three cases had mucinous carcinoma peritonei (MCP). Three cases showed MSI; one with MSH2 and MSH6 loss and two with PMS2 loss. Of the remaining four cases, KRAS mutations of codon 12 were present in three. No cases showed a BRAF mutation at codon 600.
|1||71||int||Present (PMS2 loss)||-||-||-|
|2||18||muc/SRC (f)||Negative||+ (p.G12S)||-||Present|
|3||42||muc||Present (MSH2 & MSH6 loss)||-||-||-|
|6||39||muc/SRC||Present (PMS2 loss)||-||-||Present|
|7||59||muc/SRC (f)||Negative||+ (p.G12V)||-||Present|