Differential expression of the chromosome 11 mucin genes in colorectal cancer

The four secretory mucin genes clustered on chromosome 11, MUC2, MUC5AC, MU C5B and MUC6, were screened in 37 patients with cancers in the left hemi-co lon or rectum and 10 normal rectal controls. The mucin genes were detected by ire situ hybridization using oligonucleotide probes to the variable numb er tandem repeat (VNTR) sequences, while the proteins were stained with non -VNTR (MUC2, MUC5AC and MUC5B) or VNTR (MUC6) antibodies. Low levels of MUC 2 mRNA were detected in non-mucinous adenocarcinomas (5/27) while a higher proportion of mucinous carcinomas (4/9) was positive. All 25 cases of adjac ent normal tissue expressed MUC2 mRNA. No transcripts for MUC5AC, MUC5B or MUC6 were detected in any of these specimens. MUC2 protein product was dete cted immunohistochemically in 34/36 carcinoma specimens, with no change fro m normal controls. There was de novo expression of MUC5AC in 23136 carcinom as. No MIJC5B or MUC6 protein was detected. No difference in MUC2 and MUC5A C protein was found between mucinous and non-mucinous carcinomas. The level of MUC2 was increased in moderately differentiated cancers compared with n ormal controls and decreased in the poorly differentiated group. Decreased MUC2 was found in poorly differentiated compared with moderately differenti ated tumours. More MUC5AC protein was detected in well and moderately diffe rentiated tumours than in poorly differentiated tumours and in all tumours relative to controls. The pattern of MUC2 staining in cancers was different from control tissue, with strong staining in the perinuclear region and no ne in goblet cell vesicles. MUC5AC staining was mainly detected in the cyto plasm. Poor detection of MUC2 and MUC5AC mRNA and associated strong stainin g for the total protein suggests altered biosynthesis and processing, leadi ng to the characteristic subcellular distribution. Hence, change in the syn thesis of MUC2 and the de noro appearance of MUC5AC in colorectal carcinoma s may be significant events in the adenoma-carcinoma sequence, with possibl e implications for tumour prognosis. Copyright (C) 2001 John Wiley & Sons, Ltd.