Aberrant expression and mutation of FOXQ1 in colorectal carcinoma and adenoma / 中华消化杂志

ABSTRACT

Objective To investigate the clinical pathological association of FOXQ1 with colorectal carcinoma (CRC) and colorectal adenoma (CRA). Colorectal mucosa specimens were collected between Jane 2007 and June 2009 in the First hospital of Yunnan prorince, and consisted of CRC (n=76), CRA (n=50) and normal (n=48,≥8 cm apart from cancer) tissues. Methods The expression of FOXQ1 in colorectal mucosa with was detected using immunohistochemistry (SP method). PCR amplification and direct DNA sequencing were used to identify FOXQ1 gene mutations in 23 CRC, 22 CRA and 18 normal specimens. Results There was no expression of FOXQ1 in normal specimens. Aberrant expression of FOXQ1 in either CRC or CRA specimens was significantly higher than in normal colorectal mucosa tissue (76.3% vs 0.0%, 26.0% vs 0.0% respectively, P＜0.01).Aberrant expression rates of FOXQ1 was significantly higher in CRC than that in CRA (76.3% vs 26.0%, P＜0.01). Expression level of FOXQ1 was increase gradually along with the pathological process of colorectal adenoma-carcinoma sequence. In CRC, the aberrant expression of FOXQ1 was not only distributed in nuclear of the tumor cells, but also found in the cytoplasm and the extracellular matrix. For CRC patients, the aberrant expression rates of FOXQ1 in extracellular matrix in Dukes C/D was significantly higher than that in Dukes A/B (61.5% vs 3.3%, 61.5% vs 5.0% respectively,P＜0.01);The aberrant expression of FOXQ1 in extracellular matrix in patient with lymph node metastasis was significantly higher than those without lymph node metastasis (61.5 % vs 4.0 %, P＜0.01). FOXQ1 gene mutation was only identified in one out of 23 CRC specimens, but not found in 22CRA nor 18 normal colorectal mucosa samples. Conclusions Aberrant expression of FOXQ1 may play an important role in the carcinogenesis of CRC and FOXQ1 gene may be involved in the cancer erosion and lymph node metastasis. FOXQ1 mutation is not the primary cause of aberrant FOXQ1 expression in CRC.