Immunohistochemical Study of p53 Mutation and p16, p14 Alterations Encoded by INK4a-ARF in Mucin-ypersecreting Bile Duct Tumor / 대한소화기학회지

ABSTRACT

BACKGROUND/AIMS: Mucin-hypersecreting bile duct tumor is rare, and has an unusual histologic characteristic of having various degrees of cellular atypia ranging from dysplasia to invasive carcinoma in the same specimen. To gain insight into the role of p16, p14 and p53 in the carcinogenic process of bile duct tumor, we analyzed the expression status of these proteins in mucin-hypersecreting bile duct tumor. METHODS: Immunohistochemical staining of p16, p14 and p53 were performed in 34 paraffin embedded tissues obtained from 22 patients of mucin-hypersecreting bile duct tumor. RESULTS: Thirty-four specimens were categorized into low-grade dysplasia (9), high-grade dysplasia (4), carcinoma in situ (CIS, 11) and invasive carcinoma (10) based on the degree of cytologic and structural atypia. p53 overexpressions were found in 6 (17.6%, 3 in CIS, 3 in invasive carcinoma) and more frequently observed in the advanced histologic stages (p<0.05). Loss of p16 staining was found only in 2 (6%) of low-grade dysplasia specimen. Loss of p14 staining was found in 21 (61.7%, 7 in low-grade dysplasia, 2 in high-grade dysplasia, 8 in CIS, and 4 in invasive carcinoma) and was frequently observed in low-grade and high-grade dysplasia compared to p53 (p<0.05). CONCLUSIONS: In mucin-hypersecreting bile duct tumor, p14 and p53 may play a role in the early and advanced stage of carcinogenesis, respectively. Further study regarding genetic and epigenetic alterations in p14 and p53 gene may be needed.