[838] 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.

171intPresent (PMS2 loss)---
218muc/SRC (f)Negative+ (p.G12S)-Present
342mucPresent (MSH2 & MSH6 loss)---
558mucNegative+ (p.G12C)--
639muc/SRCPresent (PMS2 loss)--Present
759muc/SRC (f)Negative+ (p.G12V)-Present

Conclusions: Like CAC, UAC can show KRAS activating mutations along with MSI and both appear mutually exclusive. Because the vast majority of our cases of UAC had mucinous histology, it was difficult to predict KRAS mutations and MSI on morphologic grounds. That stated, our three cases with KRAS mutations were mucinous histology. In our series, KRAS and MSI comprised the majority (6/7) of cases. Thus in addition to similar morphologies between CAC and UAC, our findings suggest the necessity for a CAC approach to ancillary testing for UAC. With CAC, mutations of KRAS and BRAF suggest resistance to anti-EGFR therapy. With a number of our UAC cases showing KRAS mutations, this also hints at resistance to anti-EGFR therapy. Treatment currently is non-standardized for advanced UAC and none of our patients underwent anti-EGFR therapy to correlate clinical outcome.
Category: Genitourinary (including renal tumors)

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 131, Monday Morning


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