WEDNESDAY 23RD MARCH
Authors: H Mulcahy, D Gibbons, P Mccarthy, M Duffv, N Parfrev, J Jankowskd, ) Hurst, ) Kumar, N Sheahan, Donoghue Dp O', Daf Lynch, N Mapstone, Amt Clarke, G Sobala, P Jackson, L Morrison, M Dixon, P Quirke, J Dillon, M Neilson, A Bouchier, C Hayes, ' Farrell, " Al-Bloushi, J Fielding, Larvn Ward, Robinson Chalmers, M Mcmahonu
Journal: Gut (1994)

Conventional analysis of the biological nature of oesophageal mucosa Introduction: Destruction of basement membrane is important requires multiple biopsies which may not be representative of oligoclonal during tumour spread and the progression from non-metastatic to lesions such as Barrett's metaplasia.The use of cytology potentially metastatic colorectal cancer.Urokinase-type plasminogen activator (uPA) overcomes these problems but is labour intensive and many subtle is implicated in the breakdown of the extracellular matrix, and may be morphological features are lost in the processing.In this regard application involved in cancer progression.The prognostic significance of uPA has of the molecular cell sciences can overcome these problems and in not been determined in large bowel cancer.Aim: To correlate uPA addition can elucidate earlier genetic alterations.immunohistochemical staining with clinical and pathological features, Abnormalities of differentiation characterise earlier stages of Barrett's and survival in patients with non-metastatic colorectal cancer extending tumorigenesis and we studied c-erbB3 a tyrosine kinase receptor known to beyond the bowel wall (Dukes' B).Patients: 70 patients with Dukes' B be expressed differentially in oesophageal lesions.We studied protein colorectal cancer.Mean follow-up time, 7.1 years (range, 4.9-10).expression by immunohistochemistry and Western blot analysis an RNA Methods: Formalin-fixed paraffin embedded sections were stained for expression by RT-PCR and Northern blot analysis in a range of tissue.immunohistochemistry using a monoclonal antibody against the B-chain c-erbB3 expression is strongest in Barrett's gastric-type metaplasia of uPA (American Diagnostica Inc., CT).Epithelial and stromal particularly in the differentiated compartment.In specimens with dysplasia positivity were scored independently by a pathologist blinded to clinical and those with intestinal metaplasia c-erbB3 immunoreactivity is reduced.details and patient outcome.Epithelial staining was graded as:-1) <2%;Furthermore the majority of adenocarcinomas had diminished or absent 2) 2-20%; 3) 21-50%; 4) >50%.Stromal staining was graded:-1) few immunoreactivity especially the poorly differentiated lesions.Western blot cells; 2) focal cellular aggregates; 3) multifocal aggregates; 4) diffuse.analysis confirmed the protein product corresponded with the mature c- Results: Grade 1 epithelial uPA reactivity was found in 0 cases, grade erbB3 protein of 160 kDa.2 in 5 (7%), grade 3 in 8 (12%) and grade 4 in 57 (81%).Grade 1 uPA Northern blot analysis demonstrated that the 6.4 kb c-erbB3 mRNA stromal staining was seen in 16 patients (23%), grade 2 in 22 (31%), transcript was weakly expressed even in non-dysplastic metaplasia.Using grade 3 in 19 (27%) and grade 4 in 13 (19%).A positive correlation paired primers to both 5' and 3' ends, RT-PCR confirmed that c-erbB3 between both forms of staining was seen (p=0.036).No significant mRNA in Barrett's mucosa is relatively strongly expressed and that association was found between epithelial or stromal reactivity and patient expression in dysplastic specimens and invasive neoplasia decreases age, sex, tumour site, tumour size, histological type, tumour grade, steadily and is lost in poorly differentiated lesions.vascular invasion or perineural invasion.High levels of epithelial uPA RT-PCR indicates that oesophageal cytology from dysplastic mucosa (grade 4) correlated with tumour necrosis (p=0.03).Five year survival expresses less c-erbB3 compared with non-dysplastic metaplasia.estimated by the Kaplan-Meier lifetable method was 81% for patients Brushings were taken in lcm sweeps from metaplastic epithelium during with grade 1, 2 and 3 epithelial uPA positivity (n=13) versus 58% for endoscopy and c-erbB3 was reduced or absent in cytology corresponding those with grade 4 (n=57) (Logrank analysis; p=0.01).Stromal