담관계암의 부위별 병리조직학적, 면역조직화학적 특성 및 전암 병변과의 관계

Abstract

[한글]

담관계암의 부위별 병리조직학적 특성과 면역조직화학적 특성의 차이 및 전암 병변과의 관계 등을 바탕으로 담관계 종양의 발생 기전를 밝히고자 간내 담도암 24예, 담낭암 34예, 간외담도암 51예, 담관 팽대부암 26예, 그리고 췌장암 11예 등, 총 146예의 병리조직학적 검색과 CEA, Ki-67, p53, c-erbB-2에 대한 면역조직화학적 검색을 시행하여 다음과 같은 결과를 얻었다.

1. 담관계암에서 존재한 전암 병변은 부위별로 간내 담도암에서 이형성 5예, 담낭암에서는 선종 또는 이형성이 7예, 간외 담도암에서는 선종 또는 이형성이 10예, 담관 팽대부암에서 선종 2예가 악성 병변의 주변부에 존재하였다.

2. c-erbB-2 발현 빈도는 담낭암에서 62%로 33%인 간내담도암이나 9%인 췌장암에 비해 높은 발현을 보였다. Ki-67 지수는 간외 담도암에서 19%로 14%인 간내 담도암이나 12%인 담관 팽대부암에 비해 의의있게 높았고, p53과 발현은 담관 팽대부암에서 77%로 50%인 간내 담도암이나 51%인 간외 담도암에서보다 높았다. 간외담도암에서 p53과 발현과 c-erbB-2 발현은 서로 상관관계가 있었다.

3. 전암 병변에서의 c-erbB-2 발현은 담낭암에서 29%, 간내담도암에서 20%, 간외담도암에서 10%였으며 담관 팽대부암에서는 2예 모두 관찰되지 않았다. 전암병변에서의 p53과 발현은 부위에 따라 43%에서 60%로 높게 관찰되었다.

따라서 상당수의 담관계암에서 p53 유전자의 돌연변이와 c-erbB-2 유전자의 활성이 관여하는 암발생의 기전이 있다고 생각되며 전암 병변에서도 이러한 변화가 존재하는 것으로 보아 이는 암발생 단계의 초기부터 일어난다고 생각된다.

[영문]

Biliary tract is a wide area of distinct but closely related anatomical structure which encompasses intrahepatic, gall bladder, extrahepatic, periampullary and pancreatic duct. The carcinoma of the biliary tract is fairly common in north-east Asia including Korea, but their exact histopathological characteristics and mechanisms of tumorigenesis are not well known.

To examine the differences and similarities of the histological and immunohistochemical characteristics of the biliary tract carcinomas according to their sites and to elucidate the possible mechanism of tumorigenesis, a total of 146 cases of biliary tract carcinoma including 24 intrahepatic bile duct, 34 gall bladder, 51 common bile duct, 26 periampullary and Ⅱ pancreatic carcinomas were reviewed microscopically. Immunohistochemical study using antibodies to CEA, Ki-67, p53, c-erbB-2 antigens was performed The following results were obtained.

1. Different incidence of precancerous lesions were present at the periphery of the carcinoma ; 4(20.8%) cases of dysplasia in intrahepatic bile duct carcinoma, 5 cases of adenoma and 2 cases of dysplasia(total 7 cases, 20.6%) in gall bladder carcinoma, 7 cases of adenoma, 3 cases of dysplasia(total 10 cases, 19.6%) in

common bile duct carcinoma, 2 cases of adenoma(7.7%) in periampullary carcinoma.

2. Immunohistochemically, c-erbB-2 expession in gall bladder carcinoma(62%) was significantly higher than that of intrahepatic(33%) or pancreatic carcinoma(9%). Ki-67 indices were higher in common bile duct carcinoma(19%) than those in intrahepatic(14%) or periampullary carcinoma(12%). p53 overexpression of the periampullary carcinoma(77%) was higher than that of intrahepatic(50%) or common bile duct carcinoma(51%). CEA positivity of the periampullary carcinoma(100%) was higher than that of the gall bladder carcinoma(85%). In common bile duct carcinomas, p53 overexpression correlates to the expression of the c-erbB-2.

3. c-erbB-2 exprssion was present in 29% of the precancerous 1esions of the gall bladder carcinoma, 20% of the intrahepatic, 10% of the common bile duct carcinoma and none of the 2 cases of the precancerous lesions of the periampullary carcinoma. The frequency of p53 overexpression in the precancerous lesions ranged from 43% to 60%.

These results show that a mechanism involving p53 gene mutation and c-erbB-2 gene activation is present in the tumorigenesis in a significant number of the biliary tract carcinomas. Considering that some cases of precancerous lesions such as adenoma or dysplasia also showed the same changes, it is believed that these are early events in the course of tumorigenesis of the biliary tract carcinomas.