The significance and characteristics of chromosomal abnormalities in patients with microsatellite and chromosome stable colorectal carcinoma

Objective To investigate the clinico-pathological significance and characteristics of chromosomal abnormalities in microsatellite and chromosome stable (AMCS) colorectal carcinoma (CRC). Methods Flow cytometry,microsatellite instability analysis and immunohistochemistry methods were used to examine the DNA ploidy,microsatellite instability and expression of mismatch repair proteins (hMSH_2 and hMSH_1) in 156 cases of CRCs,so as to select the MACS CRCs.Comparative genomic hybridization (CGH) method was subsequently performed to analyze the status of chromosomal abnormalities of MACS CRCs.The correlation between chromosomal changes of MACS CRC and patients clinico-pathological features was further evaluated.Results Of the 156 CRCs studied,fourty-one (26%) cases were observed both diploid/near diploid DNA content and stable microsatellite sequence and all these CRCs showed normal expression of hMSH_2 and hMSH_1 protein,and thus,defined as MACS CRC.Our CGH results showed that the overall mean numbers of chromosomal abnormality of 41 MACS CRCs was 9.6.The chromosomal arms with DNA amplification (frequency≥10%) were 20 q(68%),13 q(56%),7 q(49%),13 p(39%),20 p (37%),8 q(30%),1 q(22%),11 q(15%),16 q(12%) and 2 p,4 q,10 q(10%).The chromosomal arms with DNA deletion (frequency≥10%) were 18 q(63%),8 p(51%),17 p(37%), 1 p(30%),3 p (26%),4p,13 q,14(15%) and 21 q,Xp(10%).In addition,there was 79% and 82% MACS CRCs in Dukes' C/D stages observed amplification of 20 q and deletion of 18 q,respectively,the frequency was significantly higher that that in Dukes' A/B stages (46%,P=0.038 and 21%,P=0.0009). Conclusions The overall number of chromosomal abnormalities in MACS CRCs is similar to that of chromosomal instable (CI) CRCs,but is higher than that of microsatellite instable (MSI) CRCs.The frequent deletion of 8 p in MACS CRCs might be a special molecular event that is different from CRCs in CI and MSI pathway.Both 20 q amplification and 18 q deletion are the most frequent chromosomal abnormalities in MACS CRC and are associated closely with tumor's malignant clinical phenotype.These chromosomal changes might play important roles the development and progression of MACS CRC.