Apoptosis and its regulation in flat-type early colorectal carcinoma: comparison with that in polypoid-type early colorectal carcinoma.
OBJECTIVE
The aim of this study was to investigate the relationship among apoptotic cell death, proliferative activity, and the expression of apoptosis-regulating proteins (p53, p21 (WAF1/CIP1), and bax) in flat-type early colorectal carcinoma and to compare these factors with those in polypoid-type early colorectal carcinoma.


METHODS
Formalin-fixed, paraffin-embedded tissues of 11 flat-type early colorectal carcinomas and 17 polypoid-type early carcinomas were studied. The histologic diagnosis was either well-differentiated adenocarcinoma or carcinoma in adenoma, and the depth of invasion was limited to mucosa or submucosa. Apoptotic cells were detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling method, and proliferative activity was determined by Ki-67 immunohistochemistry using monoclonal antibody MIB-1. Apoptosis-regulating proteins were determined by immunohistochemistry using antibody DO-7 (p53), Cip1 (p21 (WAF1/CIP1)), and Bax (bax).


RESULTS
There was no significant difference in terminal deoxynucleotide transferase-mediated deoxy-uridine triphosphate-biotin nick end-labeling index between flat-type early colorectal carcinoma and polypoid-type early carcinoma, at 1.9 vs. 1.1, respectively. In flat-type carcinoma terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index in the p53 protein overexpression group was significantly smaller than that in the p53 protein-negative group (P < 0.05). The Ki-67 labeling index/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio in the p53 protein overexpression group was significantly higher than that in the p53 protein-negative group (P < 0.05). In polypoid-type carcinoma, the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index and Ki67/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio showed no significant difference between the p53 protein overexpression group and p53 protein-negative group.


CONCLUSIONS
p53-dependent apoptosis may contribute to the development of flat-type early colorectal carcinoma. Apoptosis and its regulation in flat-type early colorectal carcinoma may differ from those in polypoid-type carcinoma.
Ozawa
A
A
Department of Surgery, Jichi Medical School, Tochigi, Japan.
Konishi
F
F
Fukayama
M
M
Kanazawa
K
K
D017209:Apoptosis; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000494:pharmacology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53