Increased expression of N-myristoyltransferase in gallbladder carcinomas

BACKGROUND. Activated Src, which has intrinsic protein tyrosine kinase acti vity, has been found in human solid tumors such as colorectal and breast ca rcinomas. The Src gene encodes a cytoplasmic tyrosine kinase p60(src), whic h attaches to the inner surface of the membrane after N-terminal myristoyla tion and is implicated in transduction of signals to the nucleus. N-myristo yltransferase (NMT) catalyzes the biochemical modification process called N -myristoylation. To investigate whether, through Src, NMT contributes to th e pathogenesis of gallbladder carcinoma, the authors investigated expressio n of NMT and p53 in in situ and invasive carcinomas. METHODS, One hundred cases of documented gallbladder carcinoma were reviewe d, and 30 cases were selected randomly to evaluate expression of NMT and p5 3 by immunohistochemistry in both in situ and in invasive tumor components. RESULTS, Eighteen cases (60%) of gallbladder carcinoma showed moderate to s trong cytoplasmic positivity for NMT with increased intensity in the invasi ve component, and 12 cases (40%) were negative. The in situ component revea led mild to moderate cytoplasmic staining in 20 cases (67%), whereas the no rmal gallbladder mucosa showed weak to negative cytoplasmic staining. Moder ate to strong p53 staining was observed in 17 in situ cases (63%) and 24 in vasive cases (80%). The in situ staining patterns of p53 were unrelated to the clinical outcome of the tumor. However, moderate to strong staining of the invasive component as observed in 15 cases (50%) was associated with a mean survival of 8.8 months. Amplification of intron-8 in normal gallbladde r mucosa and invasive carcinoma were similar in intensity, suggesting the a bsence of NMT gene amplification in these tumors. CONCLUSIONS. The increased expression of NMT in these tumors could be due t o transcriptional activation. Tumors with increased expression of NMT and p 53 were associated with poor clinical outcomes as evidenced by their mean s urvival times. NMT is likely to play a pathogenic role in gallbladder carci noma. (C) 2000 American Cancer Society.