Loss of ARID1A in Uterine Endometroid Carcinoma Is Associated with Microsatellite Instability
Tsui-Lien Mao, Kuan-Ting Kuo, Ming-Chieh Lin, Li-Hui Tseng. National Taiwan University Hospital and Medical College, National Taiwan University, Taipei, Taiwan; National Taiwan University Hospital, Taipei, Taiwan
Background: ARID1A, a tumor suppressor gene participating in chromatin remodeling, has been found to be mutated in several types of human cancer. Loss of expression of ARID1A, presumably due to inactivating mutation, has been found in 26% of low-grade uterine endometrioid carcinoma (EM CA) and up to 39% to 45% in high-grade endometrioid carcinoma. However, the association with microsatellite instability (MSI) is unknown in uterine endometrioid carcinoma.
Design: Totally 23 grade 1, 7 grade 2 and 22 grade 3 uterine EM CA were included in the study. The expression of ARID1A was investigated by immunohistochemistry. Complete loss was defined as absence of ARID1A immunoreactivity in all tumor cells, whereas clonal loss was defined as lack of staining in a discrete tumor area(s) in the background of ARID1A positive tumor cells. MSI test was performed using 5 mononucleotide microsatellite loci and analyzed by capillary electrophoresis. MSI-low cases had instability in 1 microsatellite, and MSI-high cases had instability in 2 or more microsatellites.
Results: Complete and clonal loss of ARID1A was found in 5(22%) and 7(30%) of grade 1 EM CA, 2(29%) and 3(43%) of grade 2 EM CA, and 12(55%) and 1(5%) of grade 3 EM CA respectively. MSI-H was present in 7 (30%) grade 1, 4(57%) grade 2, and 10(45%) grade 3 EM CA. Correlating with ARID1A expression, MSI-H was present in 6(50%) grade 1, 4(80%) of grade 2 and 8(62%) of grade 3 tumors with complete or clonal loss of ARID1A, and in 1(9%) grade 1, 0(0%) grade 2 and 2(22%) of grade 3 tumors with retained ARID1A (p<0.0001). Three grade 3 tumors with concurrent grade 1 components had MSI test in both low-grade and high-grade components. Both components had the same MSI status in all three tumors.
Conclusions: Our study confirmed the previous finding that loss of ARID1A is more frequent in high-grade EM CA, with more tumors having complete loss than clonal loss compared to low-grade EM CA. MSI is also more prevalent in high-grade EM CA than in low-grade EM CA, and is significantly associated with tumors with loss of ARID1A expression. Loss of ARID1A and MSI may cooperate and contribute to tumor progression.
Category: Gynecologic & Obstetrics
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 203, Wednesday Afternoon