Comparative analysis of K-ras point mutation, telomerase activity, and p53 overexpression in pancreatic tumours.
K-ras point mutation, p53 over-expression, and telomerase activity have been proposed as molecular markers for clinical diagnosis of pancreatic carcinoma. To evaluate the clinical usefulness of these markers, we performed comparative analysis in 61 resected pancreatic samples including 15 intraductal papillary-mucinous tumours (IPMTs), 4 mucinous cystic tumours, 37 ductal adenocarcinomas, and five chronic pancreatitis samples. K-ras point mutation, telomerase activity, and p53 overexpression were analyzed using mutant allele specific amplification, the telomeric repeat amplification protocol, and immunohistochemical staining, respectively. In malignant tumours, K-ras mutation, telomerase activity, and p53 overexpression were detectable in 76, 91, and 46%, respectively, while in benign tumours, these alterations were detectable in 38, 0, and 0%, respectively. Among 15 IPMTs, K-ras mutation was detectable in 4 (80%) of 5 IPMT-adenomas, 4 (80%) of 5 IPMT-carcinomas and 2 (66%) of 3 papillary-mucinous carcinomas, which are invasive carcinomas derived from IPMTs. Telomerase activity was not detectable in IPMT-adenomas, but was detected in all 5 IPMT-carcinomas and 3 papillary-mucinous carcinomas. p53 overexpression was not detected in IPMTs, but was detected in 2 (66%) of 3 papillary-mucinous carcinomas, indicating that telomerase is likely to be activated concomitant with carcinogenesis. These results suggest that telomerase activity is the most useful as a differential diagnostic marker between malignant and benign pancreatic tumours.
Uemura
Kenichiro
K
Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Hiyama
Eiso
E
Murakami
Yoshiaki
Y
Kanehiro
Tetsuya
T
Ohge
Hiroki
H
Sueda
Taijiro
T
Yokoyama
Takashi
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018292:Cystadenoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation; D011379:Prognosis; D019098:Telomerase / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D019098:Telomerase