title: Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray.
abstract: OBJECTIVE
  To explore the molecular events taking place during human colon cancer development and progression through high-throughput tissue microarray analysis.
  
  
  METHODS
  We constructed two separate tissue microarrays containing 1.0 mm or 1.5 mm cylindrical samples acquired from 112 formalin-fixed and paraffin-embedded blocks, including carcinomas (n = 85), adenomatous polyps (n = 18), as well as normal para-cancerous colon tissues (n = 9). Immunohistochemical staining was applied to the analysis of the consecutive tissue microarray sections with antibodies for 11 different proteins, including p53, p21, bcl-2, bax, cyclin D1, PTEN, p-Akt1, beta-catenin, c-myc, nm23-h1 and Cox-2.
  
  
  RESULTS
  The protein expressions of p53, bcl-2, bax, cyclin D1, beta-catenin, c-myc, Cox-2 and nm23-h1 varied significantly among tissues from cancer, adenomatous polyps and normal colon mucosa (P = 0.003, P = 0.001, P = 0.000, P = 0.000, P = 0.034, P = 0.003, P = 0.002, and P = 0.007, respectively). Chi-square analysis showed that the statistically significant variables were p53, p21, bax, beta-catenin, c-myc, PTEN, p-Akt1, Cox-2 and nm23-h1 for histological grade (P = 0.005, P = 0.013, P = 0.044, P = 0.000, P = 0.000, P = 0.029, P = 0.000, P = 0.008, and P = 0.000, respectively), beta-catenin, c-myc and p-Akt1 for lymph node metastasis (P = 0.011, P = 0.005, and P = 0.032, respectively), beta-catenin, c-myc, Cox-2 and nm23-h1 for distance metastasis (P = 0.020, P = 0.000, P = 0.026, and P = 0.008, respectively), and cyclin D1, beta-catenin, c-myc, Cox-2 and nm23-h1 for clinical stages (P = 0.038, P = 0.008, P = 0.000, P = 0.016, and P = 0.014, respectively).
  
  
  CONCLUSIONS
  Tissue microarray immunohistochemical staining enables high-throughput analysis of genetic alterations contributing to human colon cancer development and progression. Our results implicate the potential roles of p53, cyclin D1, bcl-2, bax, Cox-2, beta-catenin and c-myc in development of human colon cancer and that of bcl-2, nm23-h1, PTEN and p-Akt1 in progression of human colon cancer.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China. weichangchen@126.com
authors.forename: Wei-Chang
authors.initials: WC
authors.lastname: Chen
authors.forename: Mao-Song
authors.initials: MS
authors.lastname: Lin
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Heng-Jun
authors.initials: HJ
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods*; D013194:Staining and Labeling