Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray.
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.
Chen
Wei-Chang
WC
Department of Gastroenterology, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China. weichangchen@126.com
Lin
Mao-Song
MS
Zhang
Bao-Feng
BF
Fang
Jing
J
Zhou
Qiong
Q
Hu
Ying
Y
Gao
Heng-Jun
HJ
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