BACKGROUND AND AIMS: Colorectal epithelial cells are prone to malignant transformation. Therefore, identification of differences in gene expression in the process from normal colonic crypts to @entity652 with @entity258 is essential for further insights into early tumorigenesis. To achieve this goal, a novel gene expression analysis strategy, screening for expressed transcripts in small histologically defined tissue samples, was performed. METHODS: First, laser mediated microdissection was used to isolate normal and adenomatous crypts from colonic cryosections. Then, nested RNA arbitrarily primed polymerase chain reaction (RAP-PCR) for differential display was performed to screen mRNA populations and to generate hybridisation probes for cDNA expression arrays. After evaluation of cDNA expression arrays, differential expression was confirmed at the protein level by immunohistochemistry. RESULTS: Evaluation of gene expression profiles of normal versus adenomatous colonic crypts of six different @entity1 revealed, in general, dysregulation of up to 11% of all analysed genes (total number n=588): specifically, @entity3544 - @entity5180 was upregulated in four of six @entity1 , mitogen activated protein kinase (MAPK) @entity1435 in three of six @entity1 , and interferon gamma receptor in three of six @entity1 . Conversely, @entity44586 was found to be downregulated in three of six @entity1 , @entity876 in three of six @entity1 , and @entity18180 in three of six @entity1 . CONCLUSIONS: For the first time, distinct gene expression profiles of @entity6349 areas within colonic @entity652 , using the combination of laser mediated microdissection with RAP-PCR and cDNA expression array, were shown. In these samples, upregulation of proliferation associated genes (ras-oncogene related @entity70356 and MAPK @entity1435 ) as well as downregulation of apoptosis related genes ( @entity44586 and @entity876 ) most likely reflects specific alterations in @entity652 with @entity258 . Based on upregulation of @entity70356 and MAPK @entity1435 , activation of the MAPK pathway appears to be an early event in @entity694 .

Gene expression pattern of laser microdissected colonic crypts of XXXX with @entity258 .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity44586 :: ('10922', 'Gene') :: ['FAST kinase'] @entity18180 :: ('7058', 'Gene') :: ['thrombospondin 2'] @entity3544 :: ('644914', 'Gene') :: ['p21'] @entity694 :: ('MESH:D003110', 'Disease') :: ['colonic carcinogenesis'] @entity5180 :: ('5879', 'Gene') :: ['rac1'] @entity876 :: ('7157', 'Gene') :: ['p53'] @entity70356 :: ('5879;644914', 'Gene') :: ['p21-rac1'] @entity1435 :: ('1432', 'Gene') :: ['p38alpha'] @entity652 :: ('MESH:D000236', 'Disease') :: ['adenomas'] @entity258 :: ('MESH:D009800', 'Disease') :: ['low grade dysplasia'] @entity6349 :: ('MESH:D004416', 'Disease') :: ['dysplastic']
@entity652 :: (MESH:D000236,Disease) :: ['adenomas']
