The abnormal expression of gastric M1/MUC5AC mucin in precancerous lesions and colon cancer evidenced by immunohistochemistry led us to check for its presence in the mucus obtained directly from patients undergoing surgery for cancerous (adenocarcinoma) or inflammatory (diverticulitis or ulcerative colitis) diseases. In parallel, the authors quantified aberrant crypt foci (ACF) and their immunolabelling by M1/MUC5AC in mucosae of cancer and diverticulitis patients. Immuno-Radio-Metric Assay of M1/MUC5AC mucin developed by the authors was used to detect M1/MUC5AC mucin in the colonic mucus scraped from surgical specimens. M1/MUC5AC mucin was detected in the mucus of 51/ 69 (74%) patients with colon adenocarcinoma, versus 7/27 (26%) patients with diverticulitis (threshold: 30 units of M1 mucin per mg protein, area under ROC curve: 0.80). M1/MUC5AC was present in significantly (p < 0.001) larger amounts in the mucus of cancer versus diverticulitis patients. All (10/10) patients with ulcerative colitis tested showed levels above the threshold and their mucosae were strongly labelled with the anti-M1/MUC5AC antibody by immunohistochemistry. Patients with cancer exhibited 3 fold more ACF than those with diverticulitis, but no significant difference was observed in the mean size and M1/MUC5AC expression pattern of ACF between these two groups. The expression of M1/MUC5AC was in correlation with their size. In macroscopically normal mucosa, ACF were the most important source of M1/MUC5AC mucin. Testing of M1/MUC5AC can enhance the detection of precancerous lesions and colon cancer. ' 2007 Wiley-Liss, Inc.Key words: humans; MUC5AC; colonic neoplasms; diverticulitis; ulcerative colitisThe search for specific marker of early human colon carcinogenesis focused very early on sialomucin. 1 This pioneering work led us to a better characterisation of the modification of mucin secretion evidenced by classical histologic staining. For that purpose, we developed antisera raised against gastrointestinal and ovarian mucins. 2,3 One of these antibodies against gastric mucin reacted specifically on histological sections from colon adenomas and not from normal colon, characterising a mucin we called M1. This M1 mucin was also expressed early in the rat during colon carcinogenesis induced by DMH. 4 For a better characterisation of M1 mucin, we have produced Mabs against gastric mucin by immunohistological screening method using their specific reactivity on adenoma and their nonreactivity on the normal colon. 5,6 We obtained 12 different Mabs against the gastric M1 epitopes and later demonstrated that the M1 epitopes were coded by the M1/ MUC5AC gene. 7-9 Using these antibodies, we developed an IRMA for M1/MUC5AC mucin. 10 This IRMA assay of M1/ MUC5AC mucin in pancreatic cyst fluids has been extensively used by us for the last 15 years to improve the diagnosis of mucinous cystadenoma neoplasms. 11 We also showed using immunohistochemical methods the expression of gastric M1/MUC5AC mucin in colon adenomas, hyperplastic polyps and in the ...
Aim-To determine whether pancreatitis associated protein (PAP) is a marker for cystic fibrosis which could be used in neonatal screening for the disease. Methods-PAP was assayed on screening cards from 202 807 neonates. Babies with PAP > 15 ng/ml, or > 11.5 ng/ml and immunoreactive trypsinogen (IRT) > 700 ng/ml were recalled for clinical examination, sweat testing, and cystic fibrosis transmembrane regulator (CFTR) gene analysis. Results-Median PAP value was 2.8 ng/ml. Forty four cases of cystic fibrosis were recorded. Recalled neonates (n=398) included only 11 carriers. A receiver operating characteristic curve analysis showed that PAP above 8.0 ng/ml would select 0.76% of babies, including all those with cystic fibrosis, except for one with meconium ileus and two with mild CFTR mutations. Screening 27 146 babies with both PAP and IRT showed that only 0.12% had PAP > 8.0 ng/ml and IRT > 700 ng/ml, including all cases of cystic fibrosis. Conclusion-PAP is increased in most neonates with cystic fibrosis and could be used for CF screening. Its combination with IRT looks promising. (Arch Dis Child Fetal Neonatal Ed 1999;80:F118-F122)
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