Analysis of Proliferative Activity and p53 Gene Product in the Intraepithelial Spread of Advanced Bile Duct Carcinoma

Osamu Hunato¹⁾²⁾, Tamotsu Sugai¹⁾, Noriyuki Uesugi¹⁾, Shin-ichi Nakamura¹⁾, Toru Yoshida¹⁾²⁾, Hiroyuki Nitta²⁾, Hidenobu Kawamura²⁾, Takayuki Sudo²⁾, Ryoko Sasaki²⁾ and Kazuyoshi Saito²⁾

Division of Pathology¹⁾, Central Clinical Laboratory²⁾, Department of Surgery, School of Medicine, Iwate Medical University

Introduction: Bile duct carcinoma is known to spread intraepithelially with high frequency, but biological features remain to be clarified. To differentiate clearly among biological features of the intraepithelial spread portion (IESP) and the invasive portion (IP), we studied the number of argyophilic nucleolar organizer region proteins (AgNOR), Ki-67 positive rate (Ki-67 PR), and p53 overexpression (p53 score). Methods: We stained 20 bile duct carcinoma specimens with antihuman p53 protein monoclonal antibody, antihuman Ki-67 protein monoclonal antibody by streptavidin-biotin immunoperoxidase, and AgNOR by Ploton's 1-step method. Results: Ki-67 PR was 21.5% in IESP and 20.2% in IP. AgNOR in IP was significantly larger than in IESP (IESP: 2.2, IP: 3.3, p=0.0012). Nuclear p53 immunopositivity was observed in 8 of 20 patients (40.0%) in IESP and 13 of 20 (65.0%) in IP. Cases of p53 positive stain in IP were also observed mostly in IESP. Conclusion: No difference in proliferative activity was seen between IESP and IP. This suggests that the cell kinetics of IESP are lower than in IP and that p53 overexpression plays a part in the early of carcinogenesis.

Key words
intraepithelial spread of bile duct carcinoma, invasive portion of bile duct carcinoma, cell activity, proliferative activity, p53 gene product

Reprint requests
Osamu Funato Division of Pathology, Central Clinical Laboratory, School of Medicine, Iwate Medical University 19-1 Uchimaru, Morioka, 020-0023 JAPAN

Accepted
September 25, 2002

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