title: Gene expression profiling of laterally spreading tumors.
abstract: BACKGROUND
  Laterally spreading tumors (LSTs) are generally defined as lesions >10 mm in diameter, are characterized by lateral expansion along the luminal wall with a low vertical axis. In contrast to other forms of tumor, LSTs are generally considered to have a superficial growth pattern and the potential for malignancy. We focused on this morphological character of LSTs, and analyzed the gene expression profile of LSTs.
  
  
  METHODS
  The expression of 168 genes in 41 colorectal tumor samples (17 LST-adenoma, 12 LST-carcinoma, 12 Ip [pedunculated type of the Paris classification)-adenoma, all of which were 10 mm or more in diameter] was analyzed by PCR array. Based on the results, we investigated the expression levels of genes up-regulated in LST-adenoma, compared to Ip-adenoma, by hierarchical and K-means clustering. To confirm the results of the array analysis, using an additional 60 samples (38 LST-adenoma, 22 Ip-adenoma), we determined the localization of the gene product by immunohistochemical staining.
  
  
  RESULTS
  The expression of 129 genes differed in colorectal tumors from normal mucosa by PCR array analysis. As a result of K-means clustering, the expression levels of five genes, AKT1, BCL2L1, ERBB2, MTA2 and TNFRSF25, were found to be significantly up-regulated (p < 0.05) in LST-adenoma, compared to Ip-adenoma. Immunohistochemical analysis showed that the BCL2L1 protein was significantly and meaningfully up-regulated in LST-adenoma compared to Ip-adenoma (p = 0.010). With respect to apoptosis status in LST-Adenoma, it assumes that BCL2L1 is anti-apoptotic protein, the samples such as BCL2L1 positive and TUNEL negative, or BCL2L1 negative and TUNEL positive are consistent with the assumption. 63.2 % LST-adenoma samples were consistent with the assumption.
  
  
  CONCLUSIONS
  LSTs have an unusual profile of gene expression compared to other tumors and BCL2L1 might be concerned in the organization of LSTs.
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. koshoramunemi@yahoo.co.jp.
authors.forename: Shoko
authors.initials: S
authors.lastname: Minemura
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. take197664@yahoo.co.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. araim-cib@umin.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. kenrunaway@yahoo.co.jp.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Okimoto
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. a-oyamada@live.jp.
authors.forename: Arata
authors.initials: A
authors.lastname: Oyamada
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. keiko-ueda@y3.dion.ne.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. d-maruoka@chiba-u.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Maruoka
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. matsumura919@yahoo.co.jp.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Matsumura
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. tom20852@yahoo.co.jp.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. katsuno@faculty.chiba-u.jp.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Katsuno
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. tkishi@faculty.chiba-u.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kishimoto
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. yokosukao@faculty.chiba-u.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D015854:Up-Regulation; D051020:bcl-X Protein / Q000235:genetics
chemical_list: C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; D051020:bcl-X Protein