Loss of ASXL1 expression is associated with lymph node metastasis in colorectal cancer

Abstract

Context: The function of ASXL1 in colorectal cancer ( CRC) has not been investigated yet. Aims: The purpose of this study was to investigate the clinicopathological and prognostic impact of ASXL1 expression on CRC. Settings and Design: The intensity of expression was scored as 0-3, and the extent of staining was scored as 0-4, based on the percentage of positive cells. The immunoreactivity score (IRS) was calculated by multiplying the two scores. Materials and Methods: We performed immunohistochemical staining of ASXL1 using tissue microarrays of 408 CRCs, 46 normal colonic mucosae, 48 adenomas, and 92 metastatic lymph nodes. Statistical Analysis Used: Clinicopathological variables were compared using Fisher's exact test, chi(2)-test, or unpaired Student's t-test, depending on the nature of the data. Results: A negative expression of ASXL1 was observed in 10.9% of normal mucosae, 27.1% of adenomas, 55.6% of adenocarcinomas, and 71.7% of metastatic lymph nodes (P < 0.001). With respect to the IRS cut-off score, lymph node metastasis and lymphatic invasion were more frequent in the IRS 0-6 group than in the IRS 8-12 group (56.3% vs. 33.3%, P = 0.034; 56.0% vs. 33.3%, P = 0.035). The 5-year disease-free survival rate was significantly lower in patients with IRS 0-6 group than those with IRS 8-12 group (78.7 +/- 2.5 vs. 100%, P = 0.034). Conclusion: ASXL1 might act as a tumor suppressor in CRC. The loss of ASXL1 expression might be associated with lymph node metastasis and lymphatic invasion in CRC.